Anish  Thomas, MBBS, M.D.

Anish Thomas, MBBS, M.D.

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


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

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Our key discoveries, using on a bed-to-bench-side approach to translational research (Cancer Cell 2022), 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), and (vi) discovery of extrachromosomal DNA (ecDNA) as a new mechanism that governs MYC-driven SCLC heterogeneity (Cancer Discovery, 2023).

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, three 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. Seven 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 in cancer research. Since 2015, I have served as  the Director of the NCI Medical Oncology Clinical Elective Program for medical students and residents.


Selected Recent Publications

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

Pongor LS, Schultz CW, Rinaldi L, Wangsa D, Redon CE, Takahashi N, Fialkoff G, Desai P, Zhang Y, Burkett S, Hermoni N, Vilk N, Gutin J, Rona G, Zhao Y, Nichols S, Vilimas R, Sciuto L, Graham C, Caravaca-Guasch J, Turan S, Shen T-S, Rajapakse VN, Kumar R, Upadhyay D, Kumar S, Kim YS, Roper N, Tran B, Hewitt SM, Kleiner DM, Aladjem MI, Friedman N, Hager G, Pommier Y, Ried T, Thomas A (corresponding author).
Cancer Dsicovery. 2023.
Full-Text Article
[ Journal Article ]

Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress

Thomas A (corresponding author), Takahashi N, Rajapakse V, Zhang X, Sun Y, Ceribelli M, Wilson KM, Beck E, Sciuto L, Nichols S, Schultz C, Zhang Y, Kim S, Klomp-Thomas C, McKnight C, Michael S, Aitkin Z, Redon C, Lee S, Yuno A, Lee M-J, Peer C, Wei J, Aladjem M, Figg WD, Steinberg SM, Zenke FT, Trepel JT, Pommier Y, Khan J, Thomas CJ.
Cancer Cell. 2021.
Full-Text Article
[ Journal Article ]

Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models

Lissa D, Takahashi N, Desai P, Manukyan I, Schultz C, Rajapakse V, Velez MJ, Mulford D, Roper N, Nichols S, Vilimas R, Sciuto L, Chen Y, Guha U, Rajan A, Atkinson D, El Meskini R, Weaver Ohler Z, Thomas A (corresponding author).
Nature Communications. 2021.
Full-Text Article
[ Journal Article ]

Whole exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable responses to DNA targeted therapies.

Tlemsani C, Takahashi N, Pongor L, Rajapakse VN, Tyagi M, Wen X, Fasaye G-A, Schmidt KT, Desai P, Kim C, Rajan A, Swift S, Sciuto L, Vilimas R, Webb S, Nichols S, Figg WD, Pommier Y, Calzone C, Steinberg SM, Wei JS, Guha U, Turner CE, Khan J, Thomas A (corresponding author).
Science Translational Medicine. 2021.
Full-Text Article
[ Journal Article ]

Neuroendocrine Differentiation and Efficacy of PD-1/PD-L1 Blockade in Small Cell Lung Cancer.

Roper N, Velez M, Chiappori A, Kim YS, Wei JS, Sindiri S, Takahashi N, Mulford D, Trindade C, Manukyan I, Brown AL, Trepel JB, Lee J-M, Hewitt S, Khan J, Thomas A (corresponding author).

Nature Communications. 2021.
Full-Text Article

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Physician Assistant (Contr.)
Samantha Nichols
Scientist (Contr.)
Vinod Rajapakse, Ph.D.
Research Fellow
Ajit Kumar Sharma, Ph.D.
Research Nurse Specialist
Linda Sciuto, R.N., B.S.N., O.C.N.
Research Nurse Specialist
Rasa Vilimas, R.N., B.S.N.
Yang Zhang, Ph.D.
Postdoctoral Fellow (Visiting)
Mohit Arora, Ph.D.
Postdoctoral Fellow (CRTA)
Rajesh Kumar, Ph.D.
Postdoctoral Fellow (CRTA)
Christopher Schultz, Ph.D.
Postbaccalaureate CRTA
Michael Nirula
Postbaccalaureate CRTA
Sophie Zhuang