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Anish  Thomas, MBBS, M.D.

Anish Thomas, MBBS, M.D.

  • Center for Cancer Research
  • National Cancer Institute
Senior Investigator
Developmental Therapeutics Branch

RESEARCH SUMMARY

Small-cell lung cancer (SCLC) is the most fatal and highly metastatic form of lung cancer which kills at least 200,000 people globally each year, including approximately 30,000 individuals in the United States. Most patients with advanced SCLC die within a year of their diagnosis, and less than 5% of patients survive two years. My career commitment as a medical oncologist is to improve the lives of patients with SCLC through better understanding of SCLC. Starting in 2014, we have built a new clinical and translational research program for SCLC in CCR. Using SCLC as a paradigm of aggressive cancer, we aim to understand and eventually target (i) tumor plasticity and heterogeneity (ii) metastases and (iii) chemoresistance.

Areas of Expertise

Information for Patients

Learn more about our clinical trials and the highly specialized care teams that lead them.

Research

We apply a bed-to-bench-side approach to translational research (Cancer Cell 2022). Some of our key findings include: (i) revealing replication stress as a transformative vulnerability of SCLCs characterized by high neuroendocrine differentiation (Cancer Cell 2021), (ii) providing novel insights into the genomic and transcriptomic features that render low neuroendocrine SCLC more sensitive to immunotherapy (Nat Commun 2021), (iii) validating ataxia telangiectasia and Rad3 related as a tractable SCLC target (J Clin Oncol 2018), (iv) discovery of a novel SCLC subset defined by the germline genotype and improved responses to DNA repair targeted drugs (Sci Trans Med 2021), (v) highlighting the transcriptional complexity of SCLC patient tumors in relation to patient-derived xenografts (Nat Commun 2022), (vi) and discovery of extrachromosomal DNA (ecDNA) (Cancer Discovery, 2023) and tumor microenvironment (Cell Rep Med, 2024) as drivers of SCLC heterogeneity. We are actively investigating  non-invasive methods to map SCLC heterogeneity – both genetic (Genome Med, 2025) and transcriptional (bioRxiv 2025) – using plasma-based approaches. Additionally, through the NCI rapid autopsy program, we are developing xenograft models (bioRxiv 2025) to better understand the organ-specific adaptations that drive SCLC metastasis.

Altogether, our studies have defined previously unrecognized therapeutic vulnerabilities and molecularly distinct SCLC subtypes, transforming our understanding of this disease, with implications for the care of patients with this historically recalcitrant cancer. I am an elected member of the American Society for Clinical Investigation, and my work has been recognized by the NCI Director's Award for Clinical Science, NCI Director's Award for Translational Science, NIH Award of Merit, Federal Technology Transfer Award, and the PECASE Award, the highest honor bestowed by the U.S. government on outstanding scientists and engineers beginning their independent careers.

Since 2021, four of my trainees have received the American Society of Clinical Oncology (ASCO) Young Investigator Awards, which supports high quality research conducted by early-career investigators during their transition to a faculty appointment. Several post-doctoral trainee fellows currently hold physician-scientist or Assistant Professor positions in the US, Korea, Japan, France, and Hungary. My mentees have also been recognized by the International Association for the Study of Lung Cancer (IASLC) Early Career Award, NIH Fellows Award for Research Excellence (FARE), NIH Physician-Scientist Early Investigator Award, Lasker Clinical Research Scholar Award, NCI Pathway to Independence Award for Outstanding Early Stage Postdoctoral Researchers (K99/R00), and have presented their findings at oral presentations at the World Conference on Lung Cancer (WCLC) and the American Association for Cancer Research (AACR) annual meetings. I was awarded the 2022 NCI Director’s Outstanding Mentor Award for exemplary mentoring and guidance of trainees and the 2024 NIH Postbac Distinguished Mentor of the Year Award. Since 2015, I have served as  the Director of the NCI Medical Oncology Clinical Elective Program for medical students and residents.

Publications

Selected Recent Publications

Microenvironment Shapes Small-Cell Lung Cancer Neuroendocrine States and Presents Therapeutic Opportunities.

Desai, P., N. Takahashi, R. Kumar, S. Nichols, J. Malin, A. Hunt, C. Schultz, Y. Cao, D. Tillo, D. Nousome, L. Chauhan, L. Sciuto, K. Jordan, V. Rajapakse, M. Tandon, D. Lissa, Y. Zhang, S. Kumar, L. Pongor, A. Singh, B. Schroder, A. K. Sharma, T. Chang, R. Vilimas, D. Pinkiert, C. Graham, D. Butcher, A. Warner, R. Sebastian, M. Mahon, K. Baker, J. Cheng, A. Berger, R. Lake, M. Abel, M. Krishnamurthy, G. Chrisafis, P. Fitzgerald, M. Nirula, S. Goyal, D. Atkinson, N. W. Bateman, T. Abulez, G. Nair, A. Apolo, U. Guha, B. Karim, R. El Meskini, Z. W. Ohler, M. K. Jolly, A. Schaffer, E. Ruppin, D. Kleiner, M. Miettinen, G. T. Brown, S. Hewitt, T. Conrads, and A. Thomas.
Cell Rep Med. no. 6: 2024.
Full-Text Article
[ Journal Article ]

Metastatic Organotropism in Small Cell Lung Cancer.

Krishnamurthy, M., A. Dhall, C. W. Schultz, M. A. Baird, P. Desai, J. Odell, S. Sahoo, N. Takahashi, M. Nirula, S. Zhuang, Y. Huang, B. Schroeder, Y. Zhang, M. S. Thomas, C. Redon, C. Robinson, L. Thang, L. Ileva, N. L. Patel, J. D. Kalen, A. A. Varlet, N. Zuela-Sopilniak, A. Jha, D. Wangsa, D. Butcher, T. Morgan, A. N. Afzal, R. Chari, K. Baktiar, S. Kumar, L. Pongor, S. Difilippantonio, M. I. Aladjem, Y. Pommier, M. K. Jolly, J. Lammerding, A. K. Sharma, and A. Thomas.
bioRxiv. 2024.
Full-Text Article
[ Journal Article ]

Extrachromosomal DNA Amplification Contributes to Small Cell Lung Cancer Heterogeneity and Is Associated with Worse Outcomes.

Pongor, L. S., C. W. Schultz, L. Rinaldi, D. Wangsa, C. E. Redon, N. Takahashi, G. Fialkoff, P. Desai, Y. Zhang, S. Burkett, N. Hermoni, N. Vilk, J. Gutin, R. Gergely, Y. Zhao, S. Nichols, R. Vilimas, L. Sciuto, C. Graham, J. M. Caravaca, S. Turan, S. Tsai-Wei, V. N. Rajapakse, R. Kumar, D. Upadhyay, S. Kumar, Y. S. Kim, N. Roper, B. Tran, S. M. Hewitt, D. E. Kleiner, M. I. Aladjem, N. Friedman, G. L. Hager, Y. Pommier, T. Ried, and A. Thomas.
Cancer Discovery. 13 / 4: 928-49, 2023.
Full-Text Article
[ Journal Article ]

Notch Signaling and Efficacy of Pd-1/Pd-L1 Blockade in Relapsed Small Cell Lung Cancer.

Roper, N., M. J. Velez, A. Chiappori, Y. S. Kim, J. S. Wei, S. Sindiri, N. Takahashi, D. Mulford, S. Kumar, K. Ylaya, C. Trindade, I. Manukyan, A. L. Brown, J. B. Trepel, J. M. Lee, S. Hewitt, J. Khan, and A. Thomas.
Nat Commun . 12 / 1: 3880, 2021.
Full-Text Article
[ Journal Article ]

Therapeutic Targeting of Atr Yields Durable Regressions in Small Cell Lung Cancers with High Replication Stress.

Thomas, A., N. Takahashi, V. N. Rajapakse, X. Zhang, Y. Sun, M. Ceribelli, K. M. Wilson, Y. Zhang, E. Beck, L. Sciuto, S. Nichols, B. Elenbaas, J. Puc, H. Dahmen, A. Zimmermann, J. Varonin, C. W. Schultz, S. Kim, H. Shimellis, P. Desai, C. Klumpp-Thomas, L. Chen, J. Travers, C. McKnight, S. Michael, Z. Itkin, S. Lee, A. Yuno, M. J. Lee, C. E. Redon, J. D. Kindrick, C. J. Peer, J. S. Wei, M. I. Aladjem, W. D. Figg, S. M. Steinberg, J. B. Trepel, F. T. Zenke, Y. Pommier, J. Khan, and C. J. Thomas.
Cancer Cell . 39 / 4: 566-79 e7, 2021.
Full-Text Article
[ Journal Article ]

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