Newest Lasker Clinical Research Scholar: Anish Thomas, M.D.

BY LAURA STEPHENSON CARTER

Meet the newest NIH Lasker Clinical Research Scholar: Anish Thomas whose clinical research focuses on small-cell lung cancer (SCLC), one of the most aggressive human cancers.

The Lasker Clinical Research Scholars Program, an “intramural–extramural” NIH program in partnership with the Albert and Mary Lasker Foundation, aims to grow the diminishing pool of talented physician-scientists by providing the necessary financial support to establish their careers. Lasker Scholars receive a unique combination of NIH funding for clinical research for up to 10 years. In the first phase of the program, Scholars receive appointments for five to seven years as tenure-track investigators within the NIH Intramural Research Program with independent budgets. In the second phase, successful Scholars will receive up to three years of NIH support for their research at an extramural research facility; or the Scholar can be considered to remain as an investigator within the intramural program. To learn more, go to https://www.nih.gov/research-training/lasker-clinical-research-scholars.

The following is a lightly edited version of the interview with Anish Thomas who joins 14 others in the NIH Lasker Clinical Research Scholar program.

ANISH THOMAS, M.B.B.S., M.D.

Lasker Clinical Research Scholar, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute

EDUCATION: St. John’s Medical College, Bangalore, India (M.B.B.S. and M.D.)

TRAINING: Postgraduate training, St. John’s Medical College; internal medicine residency, State University of New York Upstate Medical University (Syracuse, N.Y.); training in medical oncology at NCI and in hematology at NHLBI

CAME TO NIH: In 2013 as a fellow for training; was a staff clinician in NCI’s Thoracic and GI Oncology Branch (2013–2016); in 2016 became a staff clinician in the NCI’s Developmental Therapeutics Branch; became a Lasker Scholar in September 2017

WEBSITE: https://www.irp.nih.gov/pi/anish-thomas

Research Focus: I am a clinical researcher with a focus on small-cell lung cancer (SCLC), one of the most aggressive human cancers. The goal of my research is to systematically develop more-effective therapies for patients with SCLC and similar chemotherapy-refractory tumors by targeting key pathways involved in DNA replication, repair, and chromatin remodeling. I design and conduct phase 1 and phase 2 clinical trials that examine strategies to determine how enhancing DNA replicative stress can best be used in the clinic in combination with existing therapies to improve patient outcomes. This work stems from my intramural and extramural collaborations with basic scientists, translational researchers, surgical pathologists, and clinicians, all of whom are interested in various facets of SCLC—from understanding the biology of genomic instability, chromatin regulation, and immunomodulation in solid tumors to identifying cancer dependencies that drive responses.

How did you become interested in science and your field? I completed medical school and then went through general-medicine training (similar to a residency in the United States) in India and worked there for some time before coming to the United States. During my training in India, we would see on an average of 50 to 60 patients a day, most with infectious diseases. I was fortunate to work with Dr. Cecil Ross, one of the few people in India at the time who treated hematological cancers and bone-marrow-failure syndromes. I decided to look for additional training opportunities in the United States mainly to build on my clinical expertise and was hoping to get more involved in research.

For about a year after coming to the United States and during my residency at SUNY Upstate Medical University, I worked in the lab of former NCI researcher Bernard Poiesz. (In 1980, the year before the first cases of AIDS were reported, Poiesz, Frank Ruscetti, and colleagues at NCI discovered and characterized the first human cancer-causing retrovirus—human T-cell lymphotropic virus–type 1, HTLV-1—in a patient with leukemia/lymphoma, and they later identified HTLV-2.) []

It was my first time working in a lab, and the experience gave me an opportunity to learn its language. Although I was more fluent in the language of patient care, this experience allowed me to move and communicate easily in both worlds.

My decision to go into thoracic oncology was influenced by the exceedingly high human cost of SCLC (more people die from lung cancer each year than from colon, breast, and prostate cancers combined) and by my work with Giuseppe Giaccone, then chief of NCI’s Medical Oncology Branch. Once I decided to go into thoracic oncology, the decision to consider SCLCs was obvious. SCLC is the most lethal form of lung cancer, and other than few modifications here and there, there have been no major changes in the treatment of this cancer. What was considered state-of-the-art in the early 1980s is still state-of-the-art today. I may be naive, but I am hoping our work can make a difference.

What discoveries have you made? I have been involved in the design and conduct of some practice-changing clinical trials. One was a study of sunitinib in people with thymic cancers, which are generally fatal orphan cancers with no standard treatment options after chemotherapy fails. In our trial, sunitinib showed unprecedented responses in thymic-carcinoma patients. Based on these results, the National Comprehensive Cancer Network guidelines now recommend sunitinib for recurrent thymic carcinoma.

I was also involved with one of the first reported , the Molecular Profiling and Targeted Therapies in Advanced Thoracic Malignancies (. (Traditional clinical trials focus on a particular cancer type, but basket trials concentrate on a specific mutation.) [] We enrolled over 600 patients with chemotherapy-refractory advanced non-small-cell lung cancer, small-cell lung cancer, and thymic malignancies. Patients underwent molecular profiling of fresh or archival biopsies and were grouped by both molecular alterations and tumor histology to receive several targeted therapies. Basket trials are now used extensively in evaluating the so-called personalized-medicine hypothesis in multiple settings.

What are the advantages to working in the NIH IRP? On the patient-care front, the NIH Clinical Center offers fantastic infrastructure and facilities and an atmosphere that allows you to focus on patients without having to worry about where they are from or how they are going to pay for a test or intervention. On the research front, the NIH IRP has many experts who are potential collaborators.

What is most exciting about your work? Being able to work at the intersection of the human side of medicine and cutting-edge science. Each day is an opportunity to go back and forth between the two. It is a privilege and an inspiration to meet people—and their families—from all walks of life who are facing life-changing decisions. (Of course, you wonder what decisions you’d make under similar circumstances.) It is also enriching to be able to work closely with staff who try their best to make a positive difference. It is also great to work with scientists and clinicians who have made fundamental discoveries that have influenced the way we understand and treat cancers.

What do you like to do outside of work? I enjoy spending time with my wife and four young children.

If I had more time I would…spend more time with my family, maybe read a book, and sleep.

Would you like to tell us anything else? I am a clinician at heart and now am trying to rediscover the power of clinical observation. It was emphasized a lot during my training in India: We’d have to identify the 20-plus signs of aortic regurgitation and would have to diagnose the four different valve pathologies in a patient with rheumatic heart disease. With a combination of good clinical observation and some phenotype-to-genotype studies, I hope we can identify subsets of diseases that may be therapeutically relevant.