Improving small cell lung cancer life expectancy: Dr. Triparna Sen
Lung cancer research has made many wonderful advances in just the past few years. However, small cell lung cancer life expectancy has not increased as quickly as the non small cell lung cancer survival rate. In fact, in 2012, SCLC was included in the Recalcitrant Cancer Research Act, which called upon the National Cancer Institute to “develop scientific frameworks that will help provide the strategic direction and guidance needed to make true progress against recalcitrant or deadly cancers.”
Dr. Triparna Sen’s LCFA-funded lung cancer research is working to improve these outcomes for small cell lung cancer patients and to increase small cell lung cancer life expectancy.
Specializing in Small Cell Lung Cancer
When she was 11 years old, Triparna Sen was assigned in school to write an essay about her dreams and role models. She chose to write about Marie Curie, a physicist and chemist who conducted pioneering research on radioactivity. Triparna knew that someday, she wanted to be like Dr. Curie. Spoiler alert: her dream came true.
Born and raised in India, she is not only the first woman in her family to become a cancer researcher, but the first woman in her family to attend university. It was not an easy trajectory. There were many setbacks and hurdles from within her culture, but Dr. Sen credits those very obstacles with advancing her to where she is today: A cancer researcher with extensive experience in translational and basic research in the field of immuno-oncology, DNA damage response, and drug development. Dr. Sen is also an Assistant Attending in the Thoracic Oncology Services at Memorial Sloan Kettering Cancer Center, New York, with a joint appointment at Weil Cornell School of Medicine as an Assistant Professor.
Dr. Sen’s passion and drive are palpable, rivaled only by her profound commitment, pride, and love of her work. Specializing in Small Cell Lung Cancer (SCLC), hers is a formidable task. SCLC occurs in about 15% of all lung cancer diagnoses and is among the highest causes of cancer-related deaths, second only to pancreatic cancer. It is sneaky in that, by the time symptoms present, the disease has already metastasized. With a front-line standard treatment of chemo- and immunotherapy, initial results are usually good. The challenge is to research and develop treatment options for when the disease returns, with a vengeance, often within 6-8 months. The overall survival rate is 9-11 months with fewer than 5% surviving five years. The statistics are grim and Dr. Sen is doing everything within her power to change that.
Exceptional mentors nurture women in science
It is because of exceptional mentors that Dr. Sen, as an undergraduate physiology student, began to explore genetics, mutations, and what she refers to as the finest-tuned machine anywhere: the human body. Her PhD mentor taught her the importance of focusing on impactful research, assuring her that publications would follow (and they did!).Yet another mentor — a married mother — demonstrated the reality that one can balance life and “do it all,” raising Dr. Sen’s confidence exponentially.
For Dr. Sen, the route to becoming an award-winning research physician — her latest being The 40 Under 40 in Cancer Emerging Leaders Award — was laden with challenges. She faced discrimination, a lack of support, and difficult odds. She is quick to credit her successes and productivity (she has won more than 15 awards, 35 publications, and two patents) with having had exceptional mentors along the way.
Dr. Sen’s work on novel therapies for extensive stage small cell lung cancer life expectancy
Having won The Young Investigators Grant from LCFA, Dr. Sen is already busy working on new, and more effective protocols aimed at curing small cell lung cancer:
“Small cell lung cancer is the most aggressive form of lung cancer where chemo/immunotherapy has shown modest benefit. There is an immediate need for better therapy. My study will test novel therapies that reactivate the immune cells and make them capable of eliminating small cell lung cancer cells from the body.
In my LCFA grant, I will test the effect of novel therapies in a large integrated set of preclinical and clinical models that will magnify the impact of the work. We will test the effect of the drugs on the immune cells in patients with small cell lung cancer, which will help clinical trials.
Because government funding for research in lung cancer is far less than it should be, smaller-scale funding from organizations like LCFA plays a critical role in supporting early-career investigators — who if not for this, would face difficulty in receiving funding at all.”
Fostering the next generation of women in science
With a deep appreciation of the gifts of knowledge, support, and encouragement Dr. Sen has — in her “spare” time — mentored, and worked tirelessly to both encourage and support women’s empowerment. Among her many accomplishments, she serves as the President of The Association for Women in Science Gulf Coast Houston Chapter, an event coordinator for the New York pod of 500 Women Scientists, and an organizer for Texas Medical Center Annual Postdoctoral Career Symposium, has mentored many young women scientists, and manages to find time to paint and practice her skills as a trained classical dancer.
“I find it incredibly gratifying to be a mentor to women and minority students and am committed to fostering the next generation of women leaders.”
Dr. Sen’s work on novel therapies for small cell lung cancer patients that will enable their immune systems to expel cancer cells shows great promise to improve the outcomes and quality-of-life in patients with SCLC and to improve small cell lung cancer life expectancy overall.
LCFA/IASLC/BMS Young Investigator Award
About the LCFA-Funded Research
Dr. Sen's LCFA Funded Project
Dr. Sen’s Personal Statement
I am a lung cancer researcher with translational and basic research experience in the field of immuno-oncology, metastasis, and DNA damage response (DDR). A broad laboratory background has given me a unique perspective on targeted therapy and the integration of novel therapies into the clinic for the treatment of patients with lung cancer, especially, small cell lung cancer (SCLC). SCLC is a recalcitrant cancer in which patients initially respond well to standard of care chemotherapy, but rapidly develop resistance. Survival rates are dismal and second-line treatments are ineffective creating an urgent unmet need for understanding the biology and identifying new therapeutic targets for SCLC.
Small cell lung cancer (SCLC) is the most aggressive and metastatic form of lung cancer with an average of 33,000 new cases diagnosed in the US annually. The 2-year survival rate for advanced-stage disease is <5% and overall survival averages less than a year. There are no approved targeted therapies and chemo-immunotherapy has only shown modest activity. Thus, patients with SCLC are in desperate need of new effective treatment strategies. SCLC is one of the cancers that remains unchecked by the bodies’ immune system by decreasing expression of major histocompatibility (MHC) class I, that communicates and coordinates with the immune system to mark cells within the body that should be eliminated. In this proposal, Dr. Sen seeks to re-engage the immune system to target and eliminate SCLC cells by restoring expression of MHC class I. The preliminary data suggest that one way that SCLCs inhibit MHC class I expression is by epigenetic processes. In this proposal Dr. Sen will test this theory using complementary drug and genetic approaches to inhibit key epigenetic modifiers in preclinical models and clinical samples of SCLC to determine whether MHC class I expression is restored and immune cells capable of eliminating cancerous cells are increased at the tumor site. Since drugs targeting these pathways are already in early-stage clinical trials, the novel combination treatment strategies proposed by this work can be quickly applied to studies involving human subjects. The potential to improve outcomes and quality-of-life in patients with SCLC is immediate and widespread.
During my postdoctoral fellowship at MD Anderson Cancer Center, I demonstrated that targeting DDR proteins (CHK1, WEE1, ATR) is a viable therapeutic strategy for the treatment of SCLC. I further identified biomarkers of response and resistance to targeted therapies of SCLC (MYC and AXL). These projects honed my skills in high-throughput molecular techniques for genomic, transcriptomic, and proteomic analysis. My work supported the first Phase 2 clinical trial of the CHK1 inhibitor, LY2606268, in patients with recurrent SCLC. I further showed, for the first time, that targeting DDR promotes antitumor immunity and enhances the efficacy of programmed cell death protein 1 (PD-1) and its ligand PD-L1 blockade through stimulator of interferon genes (STING)-mediated T-cell activation in SCLC. During my postdoctoral fellowship, I also gained considerable experience in generating and characterizing circulating tumor cell-derived xenograft models of SCLC. I have collaborated with multiple academic researchers and pharmaceutical companies where I provided important data for ongoing grants and translational studies. My work has been recognized with multiple awards including the Jeffrey Lee Cousins Fellowship in Lung Cancer Research (2015 to 2018), which recognizes excellence and unique contributions to Lung Cancer Research, and the American Association for Cancer Research (AACR) Women in Cancer Research Scholar Award (2015).
In April 2019, I was recruited by Memorial Sloan Kettering Cancer Center (MSK) as an Assistant Attending and have a parallel appointment at Weil Cornell School of Medicine as an Assistant Professor. I am also the co-director of the Rudin laboratory at MSK and currently overseeing the research program, including the patient-derived xenograft library with over 300 lung cancer models. As the PI on the proposed project, I laid the groundwork for the research by robust evaluation in our established SCLC models. My experience in SCLC biology, immuno-oncology pathways, in vivo models and knowledge of how epigenetic modifiers modulates the immune microenvironment in SCLC uniquely positions me to conduct this project. My long-term goal is to rapidly translate our preclinical findings into clinical trials to meet the need for effective treatments for SCLCs that lack actionable drivers or are largely refractory to immune checkpoint blockade.