Fred Chiu-Lai Lam

All Publications

• Surgical resection versus stereotactic radiosurgery for succinate dehydrogenase-related hereditary head and neck paragangliomas. Journal of neuro-oncology Harary, P. M., Hori, Y. S., Lam, F. C., Abu-Reesh, D., Emrich, S. C., Tayag, A., Ustrzynski, L., Alyono, J., Holsinger, F. C., Dodd, R. L., Gibbs, I. C., Li, G., Park, D. J., Chang, S. D. 2026; 176 (2): 168

  View details for DOI 10.1007/s11060-025-05405-2

  View details for PubMedID 41533247

  View details for PubMedCentralID 1735225

• Artificial intelligence (AI) uses in stereotactic radiosurgery (SRS): outcome prediction with brain metastasis (BM) - A systematic review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Desai, S. P., Hori, Y. S., Kattaa, A. H., Izhar, M., Lam, F. C., Abu Reesh, D., Tayag, A., Ustrzynski, L., Emrich, S. C., Gu, X., Park, D. J., Chang, S. D. 2026; 145: 111854

  Abstract

  Brain metastases (BM) are the most common intracranial tumors in adults and present ongoing challenges in clinical management, particularly after stereotactic radiosurgery (SRS). Recent advances in artificial intelligence (AI) offer the potential to improve outcome prediction and personalize treatment. This systematic review synthesizes current literature on AI applications for prognostic modeling in BM patients undergoing SRS, with a focus on imaging-based machine learning (ML) and deep learning (DL) tools for predicting local control, survival, and treatment-related toxicity.A systematic review was performed in accordance with PRISMA guidelines. PubMed, Web of Science, and Scopus were searched in October 2024 using a targeted query combining terms related to AI, brain metastasis, and outcome prediction. After screening 255 studies and applying strict inclusion/exclusion criteria, 21 studies published between 2018 and 2024 were included. Data was extracted on study design, modeling techniques, input features, validation methods, and predictive performance.Among the 21 included studies, AI models demonstrated strong performance in predicting key outcomes following SRS. Convolutional neural networks (CNNs), recurrent neural networks, support vector machines (SVMs), and ensemble methods were widely used. Reported AUCs ranged from 0.70 to 0.98, with highest performance achieved through multimodal data integration of MRI-derived radiomic features and clinical variables. Predictive features included peritumoral edema texture, tumor margin heterogeneity, and clinical indicators such as lesion number, tumor size, and extracranial disease progression. Longitudinal modeling using serial imaging (e.g., Conv-GRU) enhanced dynamic outcome prediction. Several studies demonstrated generalizability across institutions, supporting the robustness of these models.AI models, particularly those incorporating radiomics and clinical data, show high accuracy in predicting outcomes for BM patients treated with SRS. These tools offer substantial promise for risk stratification, early identification of treatment failure, and personalized care planning. Further multicenter validation and integration into clinical workflows are warranted to fully realize the benefits of AI in SRS for brain metastases.

  View details for DOI 10.1016/j.jocn.2026.111854

  View details for PubMedID 41500171

• Radiosurgical management of pathology-proven low-grade glioma: a systematic review across the pre- and post-molecular classification era. Journal of neurosurgical sciences Mizutani, Y., Hori, Y. S., Harary, P. M., Annagiri, S., Jain, R., Liu, J., Izhar, M., Reesh, D. A., Lam, F. C., Emrich, S. C., Ustrzynski, L., Tayag, A., Park, D. J., Chang, S. D. 2025

  Abstract

  Low-grade gliomas (LGGs) are slow-growing heterogeneous tumors that remain challenging when complete resection is not feasible. While maximal safe resection remains standard, the evolving World Health Organization (WHO) classification emphasizing molecular characteristics has shifted perspectives on adjuvant therapies. In this context, the role of stereotactic radiosurgery (SRS) continues to be explored. This systematic review synthesizes literature on radiosurgical management of pathology-proven LGGs across pre- and post-molecular classification eras.A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, and Web of Science were searched in August 2024 for studies on pathology-proven LGGs treated with SRS. An additional search was performed to incorporate studies reporting molecular characteristics.Of the initially included eight studies, none reported molecular characteristics required by the 2021 World Health Organization classification, and an additional search identified one study reporting molecular characteristics, which was added to the review. Nine studies with 308 patients were included. Local control rates ranged from 66% to 94%. Several studies reported superior outcomes with surgery for recurrence, adjuvant rather than salvage SRS, and no prior radiotherapy. Adverse events were predominantly mild to moderate, including headache, dizziness, nausea, and transient neurological symptoms.SRS offers a non-invasive management option for selected LGGs with durable control and acceptable safety. Prognosis appears to be influenced by treatment history, including prior radiotherapy and surgical management. Lack of molecular stratification highlights the need for studies focused on IDH (isocitrate dehydrogenase)-mutant LGGs to clarify the role of SRS in the molecular era.

  View details for DOI 10.23736/S0390-5616.25.06656-1

  View details for PubMedID 41364089

• Efficacy and Safety of CyberKnife Stereotactic Radiosurgery for Occipital Condyle Metastasis NEUROSURGERY PRACTICE Park, D. J., Voruganti, H., Annagiri, S., Shaghaghian, E., Hori, Y. S., Persad, A. R., Yoo, K. H., Abu-Reesh, D., Lam, F. C., Tayag, A., Ustrzynski, L., Emrich, S. C., Han, S. S., Gu, X., Byun, J., Rahimy, E., Pollom, E. L., Soltys, S. G., Gephart, M., Li, G., Chang, S. D. 2025; 6 (4)

  View details for DOI 10.1227/neuprac.0000000000000169

  View details for Web of Science ID 001577502000001

• Efficacy and Safety of CyberKnife Stereotactic Radiosurgery for Occipital Condyle Metastasis. Neurosurgery practice Park, D. J., Voruganti, H., Annagiri, S., Shaghaghian, E., Hori, Y. S., Persad, A. R., Yoo, K. H., Abu-Reesh, D., Lam, F. C., Tayag, A., Ustrzynski, L., Emrich, S. C., Han, S. S., Gu, X., Byun, J., Rahimy, E., Pollom, E. L., Soltys, S. G., Gephart, M. H., Li, G., Chang, S. D. 2025; 6 (4): e000169

  Abstract

  Occipital condyle metastasis (OCM) is a rare condition characterized by severe occipital pain and neurological symptoms due to lower cranial nerve (CN) deficits, stemming from its anatomic location. Despite the widespread use of stereotactic radiosurgery (SRS) for cranial metastases, its specific impact on OCM remains underexplored. This study evaluates the efficacy and safety of CyberKnife SRS in treating OCM, focusing on occipital pain, dysfunctions of lower CNs, and local tumor control.We retrospectively analyzed cases of OCM treated with SRS at our institute from 2012 to 2023, evaluating patient demographics, presenting symptoms, treatment parameters, and outcomes.Eighteen patients (10 females) with a mean age of 64 years (SD: 10.4) were treated. Common presentations included occipital pain (44.4%) and lower CN deficits (27.8%). The median target volume was 6.95 cc (IQR: 4.64-21.2). The mean single-fraction equivalent dose was 18.7 Gy10 (SD: 1.9). Ten tumors received 15-20 Gy in 1 fraction (50%), 2 tumors received 20-28 Gy in 2 fractions (10%), 4 tumors received 27 Gy in 3 fractions (20%), and 4 tumors received 30-40 Gy in 5 fractions (20%). Based on Kaplan-Meier estimate, SRS achieved 93.8% local tumor control rate over 3 years, with a median overall survival of 13 months (95% CI: 0-32.2). Among patients presenting with symptoms, 87.5% reported occipital pain relief (P = .04), and 80% observed improvements in CN function (P = .003). Four patients experienced local recurrence.CyberKnife SRS is a promising treatment of OCM, offering significant pain relief and improvement in neurological symptoms, along with favorable local control rates. This noninvasive therapy provides a valuable alternative to surgery, potentially enhancing the quality of life for patients with limited treatment options due to this challenging condition.

  View details for DOI 10.1227/neuprac.0000000000000169

  View details for PubMedID 41163734

  View details for PubMedCentralID PMC12560716

• Treatment outcomes of cerebral arteriovenous malformations in patients with Hereditary hemorrhagic Telangiectasia: A case series from a Single-Center experience. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Izhar, M., Al Gharyani, M. F., Hori, Y. S., Kattaa, A. H., Lam, F. C., Kalra, N., Zagzoog, N., Tayag, A., Ustrzynski, L., Emrich, S. C., Park, D. J., Chang, S. D. 2025; 143: 111750

  Abstract

  Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular disorder characterized by multisystemic arteriovenous malformations (AVMs), including those in the central nervous system. Cerebral AVMs (cAVM), present in up to 23% of patients with HHT, pose a risk of serious neurological complications such as hemorrhage or seizures. Despite their clinical significance, standardized treatment guidelines for cAVM in HHT remain lacking due to limited data. This study evaluates outcomes of stereotactic radiosurgery (SRS) and microsurgical resection for unruptured cAVM in patients with HHT.We retrospectively analyzed 26 patients with clinically or genetically confirmed HHT and radiologically verified unruptured cAVM treated at our institution between 1996 and 2024. Patients were selected based on treatment with either surgery or SRS and a minimum of 1-year follow-up, excluding cases with prior ruptures or previous AVM interventions. Clinical, radiographic, and treatment data were collected and reviewed, including AVM characteristics, intervention parameters, and functional outcomes. The outcomes were changes in functional status measured by the modified Rankin Scale (mRS), complication rates, AVM obliteration, and recurrence. Statistical analysis included the X2 test, Fisher's exact test, and the Mann-Whitney U test, with significance set at p < 0.05. Survival outcomes were assessed using Kaplan-Meier analysis.Among 26 patients, 4 underwent CyberKnife SRS and 22 had microsurgical resection. In the SRS group, all patients were female with a mean age of 39 years at the time of diagnosis; 80 % of lesions achieved complete obliteration at a median follow-up of 5.9 years. Most lesions were superficial, small in volume (mean: 0.16 cm3), and received an average marginal dose of 20.1 Gy. Post-radiosurgical complications occurred in 50 %, primarily headaches and visual disturbances; no hemorrhages or seizures were reported. In the surgery group, 92 % of lesions were obliterated with a median follow-up of 2.75 years. Functional status remained stable or improved in 68 % of patients, with a significant change between pre- and postoperative scores (P = 0.03). Postoperative complications occurred in 23 % of patients, and AVM recurrence was significantly associated with SM grade (P = 0.005). No mortality was observed in either group.In patients with HHT, cAVMs are typically small, multiple, and low-grade with a low risk of hemorrhage. Both surgical resection and SRS are effective treatment options, though further prospective studies are needed to better define and compare their long-term outcomes.

  View details for DOI 10.1016/j.jocn.2025.111750

  View details for PubMedID 41237734

• A GENOME-WIDE IN VIVO CRISPR ACTIVATION SCREEN IDENTIFIES BACE1 AS A THERAPEUTIC VULNERABILITY OF LUNG CANCER BRAIN METASTASIS Chafe, S., Zhai, K., Aghaei, N., Miletic, P., Huang, Z., Brown, K., Mobilio, D., Young, D., Suk, Y., Grewal, S., Mckenna, D., Alizada, Z., Kieliszek, A., Lam, F., Escudero, L., Huang, Q., Huebner, A., Lu, J., Ang, P., Anand, A., Custers, S., Apel, E., Slassi, S., Brakel, B., Kim, J., Liu, J., Bassey-Archibong, B., Abdo, R., Shargall, Y., Lu, J., Cutz, J., Zhang, Q., Li, S., Venugopal, C., Hynds, R., Dufour, A., Moffat, J., Swanton, C., Bao, S., Singh, S. OXFORD UNIV PRESS INC. 2025: v26-v27

  View details for DOI 10.1093/neuonc/noaf201.0101

  View details for Web of Science ID 001612043500002

• Treatment outcomes for hypoglossal schwannomas: insights from a single-institution experience and literature review. Journal of neurosurgery Kattaa, A. H., Park, D. J., Persad, A. R., Hori, Y. S., Kassu, R. A., Nasta, S. R., Voruganti, H., Akhavan-Sigari, A., Lam, F. C., AbuReesh, D., Han, S. S., Emrich, S. C., Ustrzynski, L., Tayag, A., Wang, L., Gibbs, I. C., Soltys, S. G., Li, G., Adler, J. R., Chang, S. D. 2025: 1-11

  Abstract

  Hypoglossal schwannomas (HSs) are rare benign tumors originating from Schwann cells of cranial nerve XII. While surgery has been the primary treatment, stereotactic radiosurgery (SRS) is emerging as an effective alternative. This study evaluates the clinical characteristics, treatment strategies, and outcomes of HS patients managed with SRS, resection, or observation.A retrospective analysis was conducted on the medical records of HS patients treated at the authors' institution from 1999 to 2024. Collected data included demographic, clinicopathologic, radiological, and treatment details. Outcomes evaluated were local tumor control (LTC), progression-free survival, overall survival, adverse events, symptom resolution, and hypoglossal nerve deficits. A literature review adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines supplemented the analysis.The cohort included 16 patients (63% female) with 20 HS tumors. SRS was performed in 10 tumors (50%), demonstrating superior LTC (100%) over a 4- to 17-year follow-up. Symptom resolution was observed in 86% of SRS cases, and hypoglossal nerve deficits were minimized. No severe complications were reported in the SRS group, with only grade 1 adverse events noted. Resection, performed in 7 cases (35%), was associated with significant complications, including cranial nerve deficits and higher adverse event rates. The surgery group exhibited a declining LTC over time: 83% at 2 years, 63% at 4 years, and 42% at 10 years. Observation was chosen for 3 tumors (15%) with stable outcomes during follow-up.SRS provides excellent long-term control of HS with significant symptom resolution and low recurrence rates in the authors' cohort, supporting its use as a primary treatment modality in selected patients for small and medium-sized schwannomas, particularly when a minimally invasive approach is preferred.

  View details for DOI 10.3171/2025.6.JNS242975

  View details for PubMedID 41172365

• Characterizing the Microenvironment of Cerebral Arteriovenous Malformations to Test Novel Treatment Modalities. Brain sciences Wazhi, K., Lam, F. C., Guru, S., Hori, Y. S., AbuReesh, D., Shoemaker, L., Park, D. J., Chang, S. D. 2025; 15 (11)

  Abstract

  Brain arteriovenous malformations (bAVMs) consist of a tangled nidus of abnormal dilated vessels characterized by direct connections between arteries and veins that lack an intervening capillary bed, creating a high-to-low flow pressure system that is predisposed to spontaneous hemorrhage with significant associated neurologic morbidity and mortality. Treatment options for bAVMs include the following: surgical resection, intravascular embolization to obliterate blood flow through the AVM, and radiosurgery. Understanding the molecular mechanisms of bAVM formation and factors that predispose it to hemorrhage can lead to novel treatments that can improve the prognosis for patients. This review summarizes emerging insights into the complex and dynamic molecular mechanisms of bAVMs. Dysregulation in key VEGF, TGF-β/BMP9/10-ENG-ALK1-SMAD4, Notch, and MAPK/ERK signaling pathways drive abnormal angiogenesis in both syndromic and sporadic forms, with KRAS/BRAF/MAPK21 mutations specifically linked to the latter. Advances in bAVM-induced animal models have corroborated many of the genetic profiles found in humans, and they continue to provide novel insights into bAVM mechanisms. Collectively, these mechanistic findings are guiding translational advances, with targeted therapies and liquid biopsy approaches emerging as avenues for precision treatment and improved patient outcomes.

  View details for DOI 10.3390/brainsci15111145

  View details for PubMedID 41300153

  View details for PubMedCentralID PMC12650072

• Stereotactic radiosurgery for hepatitis C virus-related hepatocellular carcinoma brain metastasis: A retrospective analysis and systematic review WORLD NEUROSURGERY-X Izhar, M., Hori, Y. S., Kattaa, A. H., Lam, F. C., Kalra, N., Zagzoog, N., Tayag, A., Ustrzynski, L., Emrich, S. C., Pollom, E. L., Soltys, S. G., Gephart, M., Park, D. J., Chang, S. D. 2025; 28

  View details for DOI 10.1016/j.wnsx.2025.100541

  View details for Web of Science ID 001602623500001

• Current State-of-the-Art Animal Models of Pediatric Brain Tumors. Brain sciences Gudavalli, T., Lam, F. C., Guru, S., AbuReesh, D., Hori, Y. S., Hiniker, S., Park, D. J., Chang, S. D. 2025; 15 (10)

  Abstract

  Brain tumors are unfortunately the most common types of solid tumors in the pediatric population, superseded only by leukemias, and largely bode a poor prognosis. Despite advances in our ability to diagnose and treat pediatric brain tumors, there remains a large unmet need to develop novel therapies to improve patient outcomes. The recent understanding of the molecular drivers of oncogenesis for many of these tumors has led to the engineering of preclinical small animal models which serve as valuable tools for scientists to study the mechanisms of tumor biology, to understand interactions with the tumor microenvironment, and allow for translatable novel therapeutic discovery. This review focuses on the state-of-the art development of preclinical models of two difficult-to-treat pediatric brain tumors: (1) diffuse midline gliomas, the most lethal form of pediatric brain cancer; (2) medulloblastoma, the most common embryonal tumor of the central nervous system. We will then round off this review with a discussion on the emerging use of multi-omics and AI approaches to complement the testing of novel therapies using these in vivo animal models.

  View details for DOI 10.3390/brainsci15101104

  View details for PubMedID 41154198

• Stereotactic radiosurgery for brain metastases from non-uterine Leiomyosarcoma: A retrospective case series WORLD NEUROSURGERY-X Cardona, J. J., Hori, Y. S., Kattaa, A. H., Harary, P. M., Lam, F. C., Abu-Reesh, D., Ustrzynski, L., Emrich, S. C., Tayag, A., Hayden-Gephart, M., Park, D. J., Chang, S. D. 2025; 28

  View details for DOI 10.1016/j.wnsx.2025.100517

  View details for Web of Science ID 001572405400001

• Repeat stereotactic radiosurgery for treatment of brain metastases locally recurrent following initial radiosurgery. Journal of neuro-oncology Hall, J. C., Goel, K., Lozko, Y., Chang, S. D., Park, D. J., Hori, Y. S., Lam, F. C., AbuReesh, D., Jackson, S., Li, G., Hayden-Gephart, M., Kaneko, T., Nagpal, S., Gibbs, I. C., Rahimy, E., Byun, J., Jin, K., Pollom, E., Soltys, S. G. 2025

  Abstract

  We report outcomes of repeat stereotactic radiosurgery (rSRS) to sites of tumor progression following initial SRS. Additionally, we sought to determine if, at the time of recurrence following initial SRS, surgical resection of the tumor followed by SRS (surgery + rSRS) provided benefit compared to rSRS alone.We retrospectively reviewed patients treated with rSRS for local recurrence after initial SRS. The cumulative incidences of LF and adverse radiation effect (ARE), with death as a competing risk, were estimated.From 2004 to 2022, we identified 77 patients with 429 brain metastases treated with initial SRS, of which 97 metastases were treated with rSRS for salvage of LF following initial SRS; 49 metastases had resection prior to rSRS. Of the 429 brain metastases treated with initial SRS, the cumulative incidence of LF was 12.6% [95% confidence interval (CI) 9.7-15.9] at 1 year; in 97 sites treated with rSRS, LF was 14.6% (95%CI 8.4-22.4) at 1 year. There was no significant difference (p = 0.3) in 1-year LF after surgery + rSRS [11.1% (95%CI 4.0-22.31)] versus rSRS alone [18.4% (95%CI 9.0-30.5)]. The 1-year rates of ARE were: 3.0% (95%CI 1.7-5.0%) for initial SRS (overall grade 1-4), 15.6% (95%CI 9.2-23.6) for rSRS (overall grade 1-4), and 12.6% (95%CI 6.8-20.1%) for rSRS (symptomatic grade 2-4).Given that the 1-year local progression of 15% with rSRS is similar to the 13% of initial SRS, our data do not support that tumors recurrent after initial SRS are inherently radioresistant to salvage SRS. Tumor control must be balanced by the 1-year rates of adverse radiation effect (16% overall, 13% symptomatic).

  View details for DOI 10.1007/s11060-025-05201-y

  View details for PubMedID 40914931

  View details for PubMedCentralID 5737512

• Stereotactic radiosurgery for brain metastases from extra-renal clear cell carcinoma: A series of four patients and review of the literature. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Harary, P. M., Hori, Y. S., Kattaa, A. H., Lam, F. C., Abu-Reesh, D., Emrich, S. C., Tayag, A., Ustrzynski, L., Pollom, E. L., Park, D. J., Gephart, M. H., Chang, S. D. 2025; 141: 111602

  Abstract

  Clear cell carcinoma occurring outside of the kidney represents an aggressive histological subtype which is frequently resistant to standard chemotherapy. Brain metastases (BM) from extra-renal clear cell carcinoma (erCCC) are exceedingly rare, and the optimal treatment approach for this histology remains uncertain. To our knowledge, stereotactic radiosurgery (SRS) has not been specifically investigated for this patient population.We performed a retrospective review of patients with erCCC treated with SRS at our institution from 2003 to 2024, identifying 4 cases with a total of 13 BM. Additionally, we conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to summarize prior reports of erCCC BM. The Embase, PubMed/MEDLINE, Scopus, and Web of Science databases were queried for initial identification of records. Gray literature was additionally searched. Baseline patient characteristics, treatment modality, and treatment outcomes were extracted from reports which met inclusion criteria.The median age at initial erCCC diagnosis was 54 years, with an interval to BM ranging from 0 to 3 years. The median lesion diameter was 5.1 mm, with a median size reduction of 52.9 % at the 3-month follow-up. The local control rates were 100 %, 100 %, and 100 % at 6, 12, and 18 months, respectively. Radiation necrosis was detected in a single lesion on 18-month MRI. The mean overall survival (OS) was 23.8 months (SD: 14.5). Twenty items met the inclusion criteria for our review, 19 of which reported a single case of erCCC BM. The majority of erCCC cases were associated with the ovary, followed by those of unknown origin. Among articles reporting the stage of the primary erCCC, 64.3 % were early stage while the remaining 35.7 % were advanced stage. Surgical resection and whole-brain radiotherapy were the most common treatments, with a median OS of 7 months. Genetic characteristics were available for only 2 cases, which identified pathogenic mutations in PIK3CA (p.E545K) or BRCA2 (p.K3326*).Our case series indicates that SRS may be an effective management option for erCCC BM, demonstrating high local control rates and a favorable safety profile. Our systematic review underscores significant variability in treatment outcomes and geographical incidence of this condition, along with existing gaps in genetic characterization and neurosurgical outcomes. Given known differences in clinical behavior between erCCC and other subtypes from the same site of origin, histology-directed treatment strategies may support improved outcomes.

  View details for DOI 10.1016/j.jocn.2025.111602

  View details for PubMedID 40897159

• Stereotactic Radiosurgery for Recurrent Meningioma: A Systematic Review of Risk Factors and Management Approaches. Cancers Mizutani, Y., Hori, Y. S., Harary, P. M., Lam, F. C., Reesh, D. A., Emrich, S. C., Ustrzynski, L., Tayag, A., Park, D. J., Chang, S. D. 2025; 17 (17)

  Abstract

  Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies.

  View details for DOI 10.3390/cancers17172750

  View details for PubMedID 40940847

• Stereotactic radiosurgery for intracranial and spinal adenoid cystic carcinoma: systematic review and illustrative case presentation. Journal of neuro-oncology Cardona, J. J., Park, D. J., Al Gharyani, M. F., Wang, J. Y., Hori, Y. S., Lam, F. C., Abu-Reesh, D., Ustrzynski, L., Emrich, S. C., Tayag, A., Li, G., Gephart, M. H., Chang, S. D. 2025

  Abstract

  Adenoid cystic carcinoma (ACC) is a rare, aggressive malignancy with a predilection for perineural spread and distant metastases. Given the limited but emerging evidence on the role of stereotactic radiosurgery (SRS) in managing intracranial and spinal ACC, a systematic review was deemed necessary to synthesize relevant parameters related to clinical features and management of ACC patients, SRS treatment characteristics, and clinical outcomes across published studies.This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of the PubMed, Scopus, and Embase databases was performed to identify studies evaluating patients with histologically confirmed diagnoses of intracranial and/or spinal ACC who were treated with SRS. Additionally, a unique illustrative case was presented.A total of 129 patients and 211 lesions with ACC were identified from 16 studies published between 1992 and 2025. Patient ages ranged from 10 to 85 years. Lesions were mostly in the intracranial space (n = 194; 91.9%), followed by the spinal column (n = 17; 8.1%). Standalone SRS was administered as primary treatment in 108 lesions (57.1%). Six of eight studies documented a median prescription dose ≥ 15 Gy, while the mean calculated dose among case reports/series with individualized data was 20.8 Gy (SD = 10.4 Gy). Two of four studies recorded a median maximum tumor dose ≥ 30 Gy. Most treatment plans were delivered in a single fraction. Local tumor control (LTC) was achieved in 210/211 lesions (99.5%) over time, although 32/201 lesions eventually experienced local failure (15.9%). LTC duration ranged from 1 to 326 months, and overall survival ranged from 0 to 354 months. A 43-year-old male with concurrent intracranial and spinal ACC treated with CyberKnife SRS is presented.SRS offers favorable LTC for intracranial and spinal ACC, supporting its role as a precise, advanced radiation modality in this challenging context.

  View details for DOI 10.1007/s11060-025-05175-x

  View details for PubMedID 40699525

  View details for PubMedCentralID 11782928

• A genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis. Science translational medicine Chafe, S. C., Zhai, K., Aghaei, N., Miletic, P., Huang, Z., Brown, K. R., Mobilio, D., Young, D., Suk, Y., Grewal, S., McKenna, D., Alizada, Z., Kieliszek, A. M., Lam, F. C., Escudero, L., Huang, Q., Huebner, A., Lu, J., Ang, P., Anand, A., Custers, S., Apel, E., Slassi, S., Brakel, B., Kim, J., Liu, J. K., Bassey-Archibong, B. I., Abdo, R., Shargall, Y., Lu, J., Cutz, J., Zhang, Q., Li, S. S., Venugopal, C., Hynds, R. E., Dufour, A., Moffat, J., Swanton, C., Bao, S., Singh, S. K. 2025; 17 (805): eadu2459

  Abstract

  Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome-wide CRISPR activation screen to identify molecular drivers of brain metastasis from an orthotopic xenograft model derived from a patient with NSCLC. We found that activating expression of the Alzheimer's disease-associated beta-secretase 1 (BACE1) led to a substantial increase in brain metastases. Furthermore, genetic and pharmacological inhibition of BACE1 blocked NSCLC brain metastasis. Mechanistically, we identified that BACE1 acts through epidermal growth factor receptor to drive this metastatic phenotype. Together, our data highlight the power of in vivo CRISPR activation screening to unveil molecular drivers and potential therapeutic targets of NSCLC brain metastasis.

  View details for DOI 10.1126/scitranslmed.adu2459

  View details for PubMedID 40601773

• Radiosensitizers in Cancer Therapy: A Global Bibliometric Analysis. bioRxiv : the preprint server for biology Annagiri, S., Harary, P. M., Hori, Y. S., Lam, F. C., AbuReesh, D., Tayag, A., Ustrzynski, L., Emrich, S. C., Chang, S. D., Park, D. J. 2025

  Abstract

  Background/Objectives: Radiosensitizers are compounds given concurrently with radiotherapy to enhance the killing of cancer cells while sparing healthy tissue. Radiosensitization research has involved a diverse range of therapeutic agents. In the present study, we aimed to investigate international trends in the development of radiosensitizers across the most common cancer types.Methods: A bibliometric analysis was performed of the field of radiosensitizer research from 1956 to 2024. Individual author impacts and trends, collaborations between and productivity of countries, and themes/keywords were analyzed.Results: Our search yielded 12,690 results. The most highly represented countries were the United States of America, China, and Germany. Radiosensitizer studies for breast cancers demonstrated the highest rate of annual growth in record count by comparison with other cancer types, while publications for gynecological cancers showed the slowest growth. The most common radiosensitizers investigated included ATM kinase inhibitors, chemotherapies, gold nanoparticles, mTOR inhibitors, natural compounds such as caffeine or curcumin, and poly (ADP-ribose) polymerase inhibitors.Conclusions: The United States, Germany, and China were the most productive countries during the study period, with China demonstrating the greatest increase in annual publication rate. Additionally, pre-clinical studies primarily investigated gold particles and targeted therapies. By comparison, clinical studies focused on radiosensitizing chemotherapies.

  View details for DOI 10.1101/2025.06.26.661878

  View details for PubMedID 40667051

• Understanding the Radiobiology of Central Nervous System Diseases in the Golden Age of Radiosurgery-Does It Matter? Brain sciences Lam, F. C., Byun, J., Guru, S., AbuReesh, D., Hori, Y. S., Rahimy, E., Pollom, E. L., Soltys, S., Park, D. J., Chang, S. D. 2025; 15 (6)

  Abstract

  Stereotactic radiosurgery (SRS) deploys image-guidance to deliver multiple beams of highly focused ionizing radiation to tightly conformed anatomical targets, leading to precise dosing of radiation-induced cellular injury and predictable biological responses that can be applied to treat a multitude of central nervous system (CNS) disorders. Herein we review the principles of CNS radiobiology, comparing differences between SRS and conventional radiation therapy. We then review the radiobiology of SRS as it pertains to the treatment of CNS tumors and vascular malformations and the emerging application of SRS for the treatment of functional and psychiatric neurological disorders. Finally, we look toward the future in combining SRS with other novel technologies to improve treatment outcomes for patients with CNS disorders.

  View details for DOI 10.3390/brainsci15060649

  View details for PubMedID 40563819

• Radiosurgical management of SDHx-related paraganglioma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Harary, P. M., Hori, Y. S., Zamarud, A., Lam, F. C., Abu-Reesh, D., Emrich, S. C., Tayag, A., Ustrzynski, L., Pollom, E. L., Soltys, S. G., Li, G., Park, D. J., Chang, S. D. 2025; 138: 111387

  Abstract

  BACKGROUND AND OBJECTIVES: Paragangliomas (PGLs) are rare neuroendocrine tumors which frequently occur in the head and neck. Mutations in subunits of the succinate dehydrogenase complex (SDHx) account for approximately 50% of hereditary PGLs and are associated with increased rates of malignancy, recurrence, and multifocality. While the use of stereotactic radiosurgery (SRS) for PGLs has expanded, there is a lack of data correlating genetic background with outcomes in this distinct patient population. We aimed to evaluate the safety and efficacy of SRS, specifically long-term local control and treatment-related complications, for management of the 3 major subtypes of SDHx-related PGL.METHODS: Patients with confirmed SDHx-related PGL who underwent SRS at a single institution were retrospectively reviewed. Lesions were stratified based on location and affected SDHx gene. Primary endpoints were local control, overall survival, and symptom improvement. The secondary endpoint was treatment-related adverse events. To contextualize our results, a review of prior studies assessing SRS for head and neck PGL was performed.RESULTS: Five female and 2 male patients with SDHx mutations received SRS for 10 total PGLs during the study period. Median age at PGL diagnosis was 32years (range: 16-56), with a median age at SRS treatment of 45.5years (range: 18-59). The cohort included 2 SDHB, 1 SDHC, and 4 SDHD patients. Subtotal resection was performed for 3 of 10 lesions prior to SRS. The glomus jugulare was the most common anatomic site, followed by the carotid body and glomus vagale. Treatment volume and maximum diameter ranged from 0.3 to 30.8cm3 and 11 to 50mm, respectively. Median marginal dose was 21Gy (range: 16-25). Median follow-up was 164, 160, and 21.8months for SDHB, SDHC, and SDHD patients, respectively, with an aggregate local control rate of 100%. Symptom improvement occurred in 80% of cases with preoperative symptoms. A single patient experienced a post-SRS adverse event, late dysphagia, requiring additional treatment. Our systematic review included 9 large SRS studies reporting a total of 593 patients. Median follow-up ranged from 35 to 102months, while the median local control rate was 94.8%.CONCLUSION: To our knowledge, this represents the first analysis correlating genetic subtype of SDHx-related PGL with SRS treatment outcomes. SRS appears to provide durable local control with minimal side effects across the 3 major subtypes of SDHx-related PGL, comparable to prior reports without genetically-defined cohorts. This reaffirms its applicability as a treatment strategy for this hereditary condition.

  View details for DOI 10.1016/j.jocn.2025.111387

  View details for PubMedID 40513256

• Integrated management of metastatic spinal tumors: current status and future directions. Medical oncology (Northwood, London, England) Kim, M. J., Marianayagam, N. J., Chandra, A., Ranalli, C., Schonfeld, E., Avila-Madrigal, J. P., Flusche, A. M., Schoeffler, K., Alomari, S., Rao, N. B., Yoo, K., Lam, F. C., Park, D. J., Fanous, A. A., Chang, S. D., Lim, M., Veeravagu, A. 2025; 42 (6): 210

  Abstract

  With improved cancer survivorship, the incidence of metastatic bone disease has risen, and metastatic spinal tumors (MSTs) have emerged as a common yet significant clinical challenge. These tumors may compromise the integrity of vertebral bodies leading to pathological fractures and neurological compromise from nerve root or spinal cord compression dramatically affecting the patient's quality of life. Despite the associated morbidity and mortality, optimal treatment strategies remain elusive. Here, in our review, we provide a comprehensive analysis of the contemporary MST treatment strategies, encompassing surgical interventions, advanced radiotherapy modalities, and evolving systemic therapies including chemotherapeutic and immunotherapeutic approaches. We critically evaluate each modality's development trajectory, clinical efficacy, therapeutic advantages, and inherent limitations. Our analysis reveals a definitive shift toward precision-guided radiotherapy and minimally invasive surgical techniques that balance therapeutic efficacy with reduced morbidity. These findings underscore the necessity for multidisciplinary management and highlight promising avenues for therapeutic innovation. As treatment paradigms evolve, integration of these advanced modalities offers new hope for this vulnerable patient population facing a challenging oncological complication.

  View details for DOI 10.1007/s12032-025-02764-8

  View details for PubMedID 40366495

• Efficacy and Safety of Donut-Shaped Circumferential Spine CyberKnife Stereotactic Body Radiotherapy for Metastatic Spine Disease. Neurosurgery Park, D. J., Lee, I., Annagiri, S., Chou, K. N., Zamarud, A., Akhavan-Sigari, A., Hori, Y. S., Persad, A. R., Abu-Reesh, D., Lam, F. C., Tayag, A., Ustrzynski, L., Emrich, S. C., Gu, X., Pollom, E. L., Chang, S. D. 2025

  Abstract

  Spinal metastases (SM) with epidural spinal cord compression (ESCC) present a significant challenge because of the high risk of radiation-induced injury to critical structures such as the spinal cord and nerve roots. Traditional treatment approaches often avoid circumferential stereotactic body radiotherapy (SBRT) to reduce these risks. The efficacy and safety of donut-shaped circumferential SBRT, designed to target the spinal column while sparing the spinal cord, remains underexplored. The aim of this study was to evaluate the safety and efficacy of donut-shaped circumferential CyberKnife SBRT for SM, particularly in preventing radiation-induced myelopathy and achieving local tumor control (LTC).We retrospectively analyzed data from patients treated with donut-shaped circumferential SBRT between 2014 and 2023. Key parameters examined included patient demographics, ESCC grade (Bilsky), prior treatments, clinical symptoms, and treatment parameters. We focused on SBRT dosimetric data, radiation exposure to the spinal cord and cauda equina, adherence to dose-volume constraints, and post-SBRT outcomes, including myelopathy and LTC.Forty-eight lesions in 43 patients (median age: 65; range: 20-78) were reviewed. One patient required separation surgery for severe ESCC (Bilsky grade 3). The median clinical target volume was 63.77 cm3, and the median margin dose was 24 Gy. Over a median follow-up of 8 months, LTC was 91.1% at 6 months, 87.1% at 1 year, 82.8% at 3 years, and 62.1% at 5 years. The median overall survival was 17 months. Of the 21 lesions exceeding dose constraints, only one patient exhibited clinical myelopathy, which correlated with local tumor recurrence. No radiographic myelopathy or other radiation-induced complications were observed.Donut-shaped circumferential CyberKnife SBRT is a safe and effective treatment of SM, achieving high LTC with minimal radiation-induced complications, including myelopathy.

  View details for DOI 10.1227/neu.0000000000003446

  View details for PubMedID 40243341

• Isolated unilateral hypoglossal nerve palsy due to an atlanto-occipital juxta-articular cyst: illustrative case. Journal of neurosurgery. Case lessons Nasta, S. R., Persad, A. R., Hori, Y. S., Lam, F. C., Abu-Reesh, D., Tayag, A., Ustrzynski, L., Emrich, S. C., Dillon, W. P., El-Sayed, I. H., Chang, S. D., Park, D. J. 2025; 9 (12)

  Abstract

  Atlanto-occipital (AO) juxta-articular cysts are positioned within the hypoglossal canal, which houses the hypoglossal nerve. These cysts, whether intraneural or extraneural, can exert localized pressure on the nerve, causing isolated ipsilateral hypoglossal nerve palsy (HNP), an unusual clinical finding. The authors contribute to the scarce literature on this atypical and challenging pathology, reviewing the diagnostic complexities, preoperative indicators, key imaging features, and management strategies.A 55-year-old male presented with tongue deviation, difficulty moving his tongue, and slurring of speech. Physical examination revealed isolated right HNP. MRI showed a lobulated T2 hyperintense lesion with thin rim enhancement at the right hypoglossal canal, extending to the AO joint, suggesting a juxta-articular cyst. CT-guided cyst aspiration decompressed the lesion but yielded no fluid. The patient's symptoms temporarily improved but then were unchanged over 10 months.AO juxta-articular cysts, although rare, should be considered in the differential diagnosis of isolated HNP. High-resolution imaging is crucial for accurate diagnosis. While surgical options exist, conservative management could be appropriate depending on the clinical scenario. CT-guided cyst aspiration can provide temporary relief, but long-term improvement is uncertain. This case emphasizes the link between spinal pathology and cranial nerve dysfunction, underscoring the need for individualized treatment approaches. https://thejns.org/doi/10.3171/CASE24776.

  View details for DOI 10.3171/CASE24776

  View details for PubMedID 40127473

• Stereotactic Radiosurgery and Surgical Resection for Jugular Foramen Schwannomas: A Retrospective Comparative Study of Outcomes. Operative neurosurgery (Hagerstown, Md.) Akhavan-Sigari, A., Park, D. J., Kattaa, A. H., Hori, Y. S., Persad, A. R., AbuReesh, D., Lam, F. C., Emrich, S. C., Ustrzynski, L., Tayag, A., Chang, S. D. 2025

  Abstract

  Jugular foramen schwannomas (JFS) are rare benign tumors arising from lower cranial nerves. In this study, we aim to compare the outcomes of surgical resection (SR) and stereotactic radiosurgery (SRS) in the treatment of JFS.We conducted a retrospective analysis of 31 patients with JFS who underwent SRS (13 patients [41.9%]) or surgical resection (18 patients [58.1%]) as their primary management modality over a two-decade period. Outcomes included progression-free survival, post-treatment adverse events based on Common Terminology Criteria for Adverse Events, symptom improvement, overall survival, and the necessity for secondary interventions. Local tumor control was also evaluated in all patients who received SRS.Significant differences were observed in baseline characteristics between the SRS and SR groups, including median age (58 vs 48 years, P = .001), largest tumor diameter (32.0 vs 47.5 mm, P = .02), and total tumor volume (6.50 vs 20.5 mm3, P = .01). There were no significant differences in sex or lesion morphology (dumbbell vs nondumbbell shaped). After adjusting for baseline characteristics, no significant differences were noted in progression-free survival (90.9 vs 86.2%), overall survival (92.3 vs 100%), symptom improvement (61.5 vs 55.5%), or median Common Terminology Criteria for Adverse Events grade (1 in both groups) between the SRS and SR groups, respectively. SRS patients had significantly lower odds of requiring secondary treatment procedures after their primary intervention as compared with those who underwent SR (odds ratio = 0.02, 95% CI: 0.001-0.88, P-value = .04). Local tumor control in all SRS patients (19 patients) was 93.7% and 79.1% at six-month and five-year time points, respectively.SRS and SR demonstrate comparable effectiveness in treating JFS. However, SRS may be a more favorable option because of a reduced need for secondary interventions. Future controlled prospective studies are needed to draw more definitive conclusions.

  View details for DOI 10.1227/ons.0000000000001534

  View details for PubMedID 40116495

• Use of Carbon Fiber Implants to Improve the Safety and Efficacy of Radiation Therapy for Spine Tumor Patients. Brain sciences Lam, F. C., Guru, S., AbuReesh, D., Hori, Y. S., Chuang, C., Liu, L., Wang, L., Gu, X., Szalkowski, G. A., Wang, Z., Wohlers, C., Tayag, A., Emrich, S. C., Ustrzynski, L., Zygourakis, C. C., Desai, A., Hayden Gephart, M., Byun, J., Pollom, E. L., Rahimy, E., Soltys, S., Park, D. J., Chang, S. D. 2025; 15 (2)

  Abstract

  Current standard of care treatment for patients with spine tumors includes multidisciplinary approaches, including the following: (1) surgical tumor debulking, epidural spinal cord decompression, and spine stabilization techniques; (2) systemic chemo/targeted therapies; (3) radiation therapy; and (4) surveillance imaging for local disease control and recurrence. Titanium pedicle screw and rod fixation have become commonplace in the spine surgeon's armamentarium for the stabilization of the spine following tumor resection and separation surgery. However, the high degree of imaging artifacts seen with titanium implants on postoperative CT and MRI scans can significantly hinder the accurate delineation of vertebral anatomy and adjacent neurovascular structures to allow for the safe and effective planning of downstream radiation therapies and detection of disease recurrence. Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) spine implants have emerged as a promising alternative to titanium due to the lack of artifact signals on CT and MRI, allowing for more accurate and safe postoperative radiation planning. In this article, we review the tenants of the surgical and radiation management of spine tumors and discuss the safety, efficacy, and current limitations of CFR-PEEK spine implants in the multidisciplinary management of spine oncology patients.

  View details for DOI 10.3390/brainsci15020199

  View details for PubMedID 40002531

  View details for PubMedCentralID PMC11852773

• Coexisting sellar Rathke cleft cyst and planum sphenoidale meningioma: illustrative case. Journal of neurosurgery. Case lessons Akhavan-Sigari, A., Park, D. J., Harary, P. M., Chivakula, M., Theodros, D., Bharani, K. L., Hori, Y. S., Persad, A. R., Lam, F. C., Emrich, S. C., Ustrzynski, L., Tayag, A., Chang, S. D. 2025; 9 (3)

  Abstract

  The co-occurrence of Rathke cleft cysts (RCCs) and meningiomas in the sellar and parasellar regions represents an exceedingly rare clinical entity. Achieving maximal resection through a single operative approach while minimizing adverse events is challenging, often necessitating multiple surgical approaches, as suggested by previous reports.The authors report the case of a 49-year-old female with a history of kidney transplant who presented with headaches and was diagnosed with coexisting RCC and meningioma in the sellar and planum sphenoidale regions, respectively. Given the prolonged, refractory nature of her symptoms and based on her treatment preferences, a two-stage surgical approach was planned. This involved an endoscopic transnasal transsphenoidal approach followed by a right craniotomy to achieve maximal tumor resection while minimizing potential complications. No residual disease or tumor remnants were present at the 6-month follow-up. The pituitary gland was preserved, and the patient's preoperative symptoms had fully resolved.The preoperative diagnosis of concurrent skull base tumors is essential for effective management planning and determining the optimal surgical approach. The proximity of these tumors to critical neurovascular structures necessitates meticulous surgical planning to minimize adverse effects while ensuring maximal tumor resection. https://thejns.org/doi/10.3171/CASE24551.

  View details for DOI 10.3171/CASE24551

  View details for PubMedID 39832313

• "Beyond the Knife"-Applying Theranostic Technologies to Enhance Outcomes in Neurosurgical Oncology. Brain sciences Guru, S., Lam, F. C., Akhavan-Sigari, A., Hori, Y. S., AbuReesh, D., Tayag, A., Emrich, S. C., Ustrzynski, L., Park, D. J., Chang, S. D. 2024; 14 (12)

  Abstract

  The current standard of care for brain tumor management includes maximal safe surgical resection followed by concurrent chemotherapy and radiation therapy. Recent advances in image-guided surgical techniques have enhanced the precision of tumor resections, yet there remains a critical need for innovative technologies to further improve patient outcomes. Techniques such as fluorescence image-guided neurosurgery in combination with stereotactic radiosurgery have improved outcomes for patients with brain tumors. In this article for Brain Science's Special Issue Recent Advances in Translational Neuro-Oncology, we review the use of image-guided neurosurgery and stereotactic radiosurgery for the treatment of brain tumors. In addition, we summarize the emerging use of theranostic nanoparticles for the delivery of diagnostic and therapeutic technologies to enable the neurosurgeon to perform more precise surgical resections in the operating room, to specifically target the delivery of existing and novel treatments to tumor cells, and to augment the efficacy of stereotactic radiosurgery. These innovative translational tools will allow neurosurgeons, neuro-oncologists, and radiation oncologists to go "beyond the knife" to improve the survival of brain tumor patients.

  View details for DOI 10.3390/brainsci14121253

  View details for PubMedID 39766452

  View details for PubMedCentralID PMC11674837

• "Beyond the Knife"-Applying Theranostic Technologies to Enhance Outcomes in Neurosurgical Oncology BRAIN SCIENCES Guru, S., Lam, F. C., Akhavan-Sigari, A., Hori, Y. S., Abureesh, D., Tayag, A., Emrich, S. C., Ustrzynski, L., Park, D. J., Chang, S. D. 2024; 14 (12)

  View details for DOI 10.3390/brainsci14121253

  View details for Web of Science ID 001386741300001

• BRD4 prevents the accumulation of R-loops and protects against transcription-replication collision events and DNA damage NATURE COMMUNICATIONS Lam, F. C., Kong, Y., Huang, Q., Vu Han, T., Maffa, A. D., Kasper, E. M., Yaffe, M. B. 2020; 11 (1): 4083

  Abstract

  Proper chromatin function and maintenance of genomic stability depends on spatiotemporal coordination between the transcription and replication machinery. Loss of this coordination can lead to DNA damage from increased transcription-replication collision events. We report that deregulated transcription following BRD4 loss in cancer cells leads to the accumulation of RNA:DNA hybrids (R-loops) and collisions with the replication machinery causing replication stress and DNA damage. Whole genome BRD4 and γH2AX ChIP-Seq with R-loop IP qPCR reveals that BRD4 inhibition leads to accumulation of R-loops and DNA damage at a subset of known BDR4, JMJD6, and CHD4 co-regulated genes. Interference with BRD4 function causes transcriptional downregulation of the DNA damage response protein TopBP1, resulting in failure to activate the ATR-Chk1 pathway despite increased replication stress, leading to apoptotic cell death in S-phase and mitotic catastrophe. These findings demonstrate that inhibition of BRD4 induces transcription-replication conflicts, DNA damage, and cell death in oncogenic cells.

  View details for DOI 10.1038/s41467-020-17503-y

  View details for Web of Science ID 000564154300005

  View details for PubMedID 32796829

  View details for PubMedCentralID PMC7428008