Dr. Triparna Sen is an Assistant Attending, Department of Medicine, Memorial Sloan Kettering Cancer Center; Assistant Professor, Weil Cornell School of Medicine
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.
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.
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.