Mobeen Rahman

All Publications

• Case report: Dramatic impact of DNA next generation sequencing results using specific targeted therapies-ALK and PIK3CA. Frontiers in oncology Cullum, S., Vang, H., Glover, M., Alammarah, H., Morton, H., Pham, N., Rahman, M., Khan, S. A. 2024; 14: 1462930

  Abstract

  In the era of targeted therapies, the clinical importance and utility of next-generation sequencing (NGS) has expanded significantly. Owing to the relative ease and financial feasibility of NGS, the use of personalized treatment strategies has the potential to revolutionize cancer care. In this case report, we explored the use of NGS in salivary gland carcinoma (SGC) and spindle cell neoplasm of the scalp. In our patient with SGC, NGS revealed a GPHN-ALK variant that allowed off-label treatment with alectinib, with a remarkable response in primary and metastatic foci. Similarly, the use of NGS in a cutaneous neoplasm in which no definitive diagnosis could be reached by pathology and which had progressed through standard of care treatment elucidated a PIK3CA mutation in which alpelisib was added and ultimately halted POD. Here, we discuss the use of NGS, future projections, and our recommendations.

  View details for DOI 10.3389/fonc.2024.1462930

  View details for PubMedID 39659799

  View details for PubMedCentralID PMC11628483

• Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy. Genes & development Guan, L., Viswanathan, V., Jiang, Y., Vijayakumar, S., Cao, H., Zhao, J., Colburg, D. R., Neuhöfer, P., Zhang, Y., Wang, J., Xu, Y., Laseinde, E. E., Hildebrand, R., Rahman, M., Frock, R., Kong, C., Beachy, P. A., Artandi, S., Le, Q. T. 2024

  Abstract

  Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of "cell cycling" and "oxidative stress response" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.

  View details for DOI 10.1101/gad.351577.124

  View details for PubMedID 38997156

• Promising Therapeutic Targets for Recurrent/Metastatic Anaplastic Thyroid Cancer. Current treatment options in oncology Abdalla, A. S., Rahman, M., Khan, S. A. 2024

  Abstract

  Anaplastic thyroid cancer presents formidable challenges, particularly in cases of recurrence or metastasis. Timely BRAF V600E testing is imperative at diagnosis, initially through immunohistochemistry, followed by comprehensive genomic profiling encompassing genes such as NTRK, RET, ALK, and assessment of tumor mutation burden (TMB). FDA-approved treatment options include dabrafenib and trametinib for patients with BRAF mutations, while those exhibiting high TMB may benefit from pembrolizumab. Further therapeutic decisions hinge upon mutational profile, urgency of response required, airway integrity, and access to targeted therapies There is growing use of immunotherapy for ATC based on published reports of activity, but currently there is no FDA approved agent for ATC. The off-label utilization of "precision medicine" combinations imposes a considerable financial strain, underscoring the necessity for further clinical trials to elucidate promising therapeutic avenues for this orphan disease. There is a pressing need for the development and support of clinical trials investigating genomically driven and immune-based therapies for anaplastic thyroid cancer.

  View details for DOI 10.1007/s11864-024-01219-y

  View details for PubMedID 38862695

  View details for PubMedCentralID 8216772

• A Novel Gene Fusion YLPM1::PRKD1 Identified in a Cribriform Subtype of Polymorphous Adenocarcinoma. Head and neck pathology Miyakawa-Liu, M., Ozawa, M. G., Chen, M., Rahman, M. 2024; 18 (1): 43

  Abstract

  Cribriform adenocarcinoma of the salivary gland (CASG) is an entity that is currently classified under polymorphous adenocarcinoma (PAC), cribriform subtype per the 2022 WHO classification of head and neck tumours. There is debate about whether CASG should be considered a separate diagnostic entity, as CASG differs from conventional PAC in anatomic site, clinical behaviors, and molecular patterns. Herein we describe a challenging and unique case which shares histologic and behavioral features between CASG and conventional PAC with a YLPM1::PRKD1 rearrangement not previously reported in the literature.

  View details for DOI 10.1007/s12105-024-01648-z

  View details for PubMedID 38735907

  View details for PubMedCentralID 7863585

• How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck. Head & neck Miller, A., Wang, V., Jegede, V., Necker, F., Curry, J., Baik, F. M., Verma, A., Holsinger, F. C., Tuluc, M., Rahman, M., Lewis, J. S., Rosenthal, E., Topf, M. C. 2024

  Abstract

  Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy.Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave).A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins.Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

  View details for DOI 10.1002/hed.27793

  View details for PubMedID 38702976

• Patient With Dysphonia. JAMA otolaryngology-- head & neck surgery Ng, C. H., Rahman, M., Damrose, E. J. 2024

  Abstract

  A male individual in his 60s had presented with a hoarse and weak voice and a history of follicular lymphoma with multiple relapses treated with an allogeneic stem cell transplant complicated by graft-vs-host disease treated with sirolimus and steroids. What is your diagnosis?

  View details for DOI 10.1001/jamaoto.2024.0057

  View details for PubMedID 38451545