Isabel Jabara

All Publications

• Urine cell-free RNA for bladder cancer detection and treatment response prediction. Nature medicine Liu, K. J., Shi, W. Y., Nesselbush, M. C., Phillips, N. A., Mach, K. E., Luca, B., Bajpai, R. K., Jabara, I., Cheng, J. C., Sugio, T., Shukla, N., Shen, E. C., Koh, I. L., Wu, D. J., Liu, C. L., Almanza, D., Jun, S., Tian, F., Hamilton, E. G., Hoerner, C. R., Wang, R., Esfahani, M. S., Hui, A., La, V., Holton, G., Rodriguez, G., Lee, T. J., Ling, X., Kalahasti, N., Vallamkonda, S., Mullane, P., Chen, S. B., Shkolyar, E., Prado, K., Khaki, A. R., Chan, E., Buyyounouski, M. K., Fan, A. C., Skinner, E. C., Alizadeh, A. A., Liao, J. C., Diehn, M. 2026

  Abstract

  Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette-Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.

  View details for DOI 10.1038/s41591-026-04673-3

  View details for PubMedID 42827132

  View details for PubMedCentralID 10531979

• Cell-free RNA changes precede symptomatic radiation pneumonitis in cancer patients receiving thoracic radiotherapy Jabara, I., Kastelowitz, N., Nesselbush, M., Phillips, N., Binkley, M. S., Bonilla, R. F., Liu, K., Jiang, A., Kovalchuk, N., Alizadeh, A. A., Diehn, M. AMER ASSOC CANCER RESEARCH. 2026

  View details for DOI 10.1158/1538-7445.AM2026-5270

  View details for Web of Science ID 001734462700010

• Field-effect-informed urine liquid biopsy for bladder cancer. Cell Shi, W. Y., Liu, K. J., Esfahani, M. S., Mach, K. E., Phillips, N. A., Almanza, D., Bajpai, R. K., Schroers-Martin, J. G., Trabanino, L., Lee, T. J., La, V., Rodriguez, G., Holton, G., Chen, S. B., Mullane, P., Wu, D. J., Nesselbush, M. C., Sugio, T., Cheng, J. C., Jabara, I., Hamilton, E. G., Alig, S. K., Liu, C. L., Peterson, D. J., Prado, K., Shkolyar, E., Thong, A., Shah, J. B., Gill, H., Kunder, C. A., Chan, E., Khaki, A. R., Skinner, E. C., Alizadeh, A. A., Liao, J. C., Diehn, M. 2026

  Abstract

  Only some non-muscle-invasive bladder cancer (NMIBC) patients benefit from intravesical Bacillus Calmette-Guérin (BCG), and predictive biomarkers remain lacking. While urine tumor DNA (utDNA) analysis is promising, mutations in tumor-adjacent normal urothelium, namely the field effect, limit specificity. Here, we show that the prevalence of somatic mutations in the urine increases with age. We introduce an improved utDNA minimal residual disease (MRD) approach that increases specificity by removing field-effect mutations. Applying this field-effect-informed MRD approach to 261 samples from NMIBC patients undergoing surgery and adjuvant BCG, we identify three molecular response classes, including surgical responders, BCG responders, and non-responders. Molecular predictors of response to the two treatments differ, with pre-existing immune activation and higher mutation burden enriched in BCG but not surgery responders. These findings highlight the potential of field-effect-informed liquid biopsy methods for guiding personalized therapy and uncovering biomarkers for individual components of multimodal treatments.

  View details for DOI 10.1016/j.cell.2025.12.054

  View details for PubMedID 41605210

• Phase 2 study of amivantamab plus lazertinib in previously-treated patients with EGFR mutant lung cancers with brain and leptomeningeal metastases. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Chen, M. F., Lee, J. J., Choudhury, N. J., Hui, A. B., Jeng, M. Y., Zheng, J., Aly, R. G., Sielski, N., Ahn, L., Pupo, A., Nesselbush, M. C., Jabara, I., Wilcox, J. A., Santomasso, B. D., Lin, A. L., Schaff, L., Chaft, J. E., Riely, G. J., Kris, M. G., Arfe, A., Yang, S. R., Young, R. J., Diehn, M., Boire, A., Yu, H. A. 2025

  Abstract

  Despite improved central nervous system (CNS) disease control with osimertinib, 20% of patients will develop CNS progression. Amivantamab and lazertinib have demonstrated activity in patients with EGFR-mutant lung cancer. This trial evaluated amivantamab and lazertinib in patients with new or progressive CNS metastases after prior therapy (NCT04965090).We evaluated amivantamab and lazertinib in 2 cohorts: patients with 1) brain metastases (BrM) or 2) leptomeningeal disease (LMD) diagnosed by cytology in patients with lung cancers with sensitizing EGFR-activating mutations or exon 20 insertions. The primary endpoint was composite best overall response rate (ORR) per RECIST v 1.1 and RANO-BM or -LM. Secondary endpoints were toxicity, systemic ORR, CNS ORR, time on treatment (ToT), progression-free survival (PFS), CNS PFS, and overall survival (OS).We treated 20 pts with BrM and 21 pts with LMD. 41% had EGFR del19, 37% L858R, 12% ex20ins, and 10% uncommon mutations. Median lines of prior therapy: 2 (range 1-7). The ORR by a combination of RECIST and RANO-BM/RANO-LM respectively for pts with BrM was 50% (95% CI, 27-73%) and 33% (95% CI, 15-57%) for pts with LMD. The median PFS was 5.8 months (95% CI 3.6-not reached (NR)) and 7.8 months (95% CI 4.2-12.2) for the BrM and LMD cohorts respectively. Median OS was 17.4 months (15.4-NR) in the BrM cohort and 14.4 months (8.9-NR) in the LMD cohort.Amivantamab+lazertinib has anti-tumor activity in patients with EGFR-mutant lung cancers who develop new or progressing brain or leptomeningeal metastases. This trial demonstrates the feasibility of including patients with LMD in prospective clinical trials.

  View details for DOI 10.1016/j.jtho.2025.10.012

  View details for PubMedID 41139066

• An ultrasensitive method for detection of cell-free RNA. Nature Nesselbush, M. C., Luca, B. A., Jeon, Y. J., Jabara, I., Meador, C. B., Garofalo, A., Binkley, M. S., Hui, A. B., van 't Erve, I., Xu, N., Shi, W. Y., Liu, K. J., Sugio, T., Kastelowitz, N., Hamilton, E. G., Liu, C. L., Olsen, M., Bonilla, R. F., Wang, Y. P., Jiang, A., Lau, B., Eichholz, J., Banwait, M., Schroers-Martin, J., Boegeholz, J., King, D. A., Luikart, H., Esfahani, M. S., Mehrmohamadi, M., Stehr, H., Raclin, T., Tibshirani, R., Khush, K., Srinivas, S., Yu, H., Rogers, A. J., Nair, V. S., Isbell, J. M., Li, B. T., Piotrowska, Z., Sequist, L. V., Hata, A. N., Neal, J. W., Wakelee, H. A., Gentles, A. J., Alizadeh, A. A., Diehn, M. 2025

  Abstract

  Sensitive methods for detection of cell-free RNA (cfRNA) could facilitate non-invasive gene expression profiling and monitoring of diseases1-6. Here we describe RARE-seq (random priming and affinity capture of cfRNA fragments for enrichment analysis by sequencing), a method optimized for cfRNA analysis. We demonstrate that platelet contamination can substantially confound cfRNA analyses and develop an approach to overcome it. In analytical validations, we find RARE-seq to be approximately 50-fold more sensitive for detecting tumour-derived cfRNA than whole-transcriptome RNA sequencing (RNA-seq), with a limit of detection of 0.05%. To explore clinical utility, we profiled 437 plasma samples from 369 individuals with cancer or non-malignant conditions and controls. Detection of non-small-cell lung cancer expression signatures in cfRNA increased with stage (6 out of 20 (30%) in stage I; 5 out of 8 (63%) in stage II; 10 out of 15 (67%) in stage III; 80 out of 96 (83% sensitivity) in stage IV at 95% specificity) and RARE-seq was more sensitive than tumour-naive circulating tumour DNA (ctDNA) analysis. In patients with EGFR-mutant non-small-cell lung cancer who developed resistance to tyrosine kinase inhibitors, we detected both histological transformation and mutation-based resistance mechanisms. Finally, we demonstrate the potential utility of RARE-seq for determination of tissue of origin, assessing benign pulmonary conditions and tracking response to mRNA vaccines. These results highlight the potential value of ultrasensitive cfRNA analysis and provide proof of concept for diverse clinical applications.

  View details for DOI 10.1038/s41586-025-08834-1

  View details for PubMedID 40240612

  View details for PubMedCentralID 8060291

• A phase 2 study of amivantamab plus lazertinib in patients with <i>EGFR</i>-mutant lung cancer and active central nervous system disease Yu, H., Chen, M. F., Hui, A. B., Choudhury, N. J., Lee, J., Zheng, J., Ahn, L., Pupo, A., Nesselbush, M., Jabara, I., Heller, G., Arbour, K. C., Santini, F., Offin, M., Chaft, J. E., Young, R. J., Riely, G. J., Kris, M. G., Diehn, M., Boire, A. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402015