Lung Cancer

The overall principal investigators and co-directors of this HCC SPORE proposal are Dr. Lecia Sequist, MD, MPH and Dr. David Barbie, MD. This selection was based on Drs. Sequist and Barbie’s outstanding and highly accomplished track records as collaborative investigators within the HCC Lung Cancer Program who bring complementary strengths and leadership abilities to the SPORE. Their leadership cements and ensures the integration of two of the key HCC member institutions – MGH and DFCI. From a scientific perspective, Dr. Sequist and Dr. Barbie also provide the ideal balance of complementary interests and expertise.

As detailed further below, Dr. Sequist has devoted much of her career to translational research in EGFR-mutant lung cancer and has recently become leader of the newest research program housed within HCC, the Program for Cancer Risk, Prevention, and Early Detection. Meanwhile, Dr. Barbie is a leading basic science and translational expert in lung cancer immunotherapy, also recently named as Associate Director of the Dana-Farber Belfer Center for Applied Cancer Science. His research focus complements that of Dr. Sequist’s, tackling treatment refractory KRAS mutant and small cell lung cancers from the perspective of innate immunity.

Their joint leadership blends strengths in clinical investigation, lung cancer prevention, and translational immuno-oncology, thus providing an ideal and complementary balance to address key areas of focus in this application that are critical to improving lung cancer cures. Finally, Drs. Sequist and Barbie are both known for being generous of their time and efforts, genuine in their support of colleagues from across HCC and outside of Harvard alike, and committed to helping the HCC Lung Program become stronger and more integrated over the coming years.

Drs. Sequist and Barbie both have a proven track record of integral collaborations within their institutions, across institutions, and more globally.

Dr. Lecia Sequist is The Landry Family Professor of Medicine at Harvard Medical School and has led many successful collaborative efforts that have brought together teams from across our own institutions, as well as nationally and internationally to accomplish high impact research in her dual areas of interest: targeted therapeutics for lung cancer and lung cancer screening/early detection.

She began her career in 2004 organizing the first prospective trial of EGFR-mutation screening and treatment in the US, organizing a consortium of 10 centers to accomplish this. She then went on to lead several national and international clinical trials, most notably the LUX-Lung trial that led to FDA approval of afatinib, the original study of rocelitinib, and the TATTON combination study of osimertinib and savoltinib. Her translational research has focused on repeat biopsies at acquired resistance and she has been a pioneer in studying adenocarcinoma-to-small cell lung cancer transformations among EGFR patients. She has been the primary mentor during training for a number of leading clinical/translational researchers in the field including Drs. Nate Pennell (Cleveland Clinic), Joel Neal (Stanford), Sarah Goldberg (Yale), and Zofia Piotrowska (MGH).

She also mentors investigators from a variety of institutions through her work with organizations such as LUNGevity, ECOG, ASCO and the International Association for the Study of Lung Cancer (IASLC), to which she was just elected to the Board or Directors. In the realm of early detection, Dr. Sequist led a SU2C Interception team together with Dr. Max Diehn from Stanford that showed the promise of the CAPP-Seq circulating tumor DNA (ctDNA) technology in early detection and has worked closely with investigators from a broad range of disciplines such as radiology, surgery, pathology, epidemiology and engineering (including Massachusetts Institute of Technology, MIT) in recent years to start both the Center for Innovation in Early Cancer Detection at MGH and the HCC program in Cancer Risk, Prevention and Early Detection. She has been funded by the NIH, DOD, SU2C, LUNGevity, American Lung Association and Lung Cancer Research Foundation.

She has experience running successful institutional granting programs as the PI of the MGH American Cancer Society Internal Research Grant program and the MGH T32 training grant (together with Dr. Daniel Haber), among others. Her leadership roles and involvement at a variety of organizations including ASCO, IASLC, AACR, ECOG, LUNGevity, American Lung Association, Stand Up 2 Cancer, and others will be critical to enabling the research findings generated by this SPORE to amplify through both horizontal and vertical collaborations with other groups and especially other lung cancer SPORES. She currently serves on the NCI Thoracic Malignancy Steering Committee, the External Advisory Board for the Oregon Health Sciences University Knight Cancer Center’s Early Detection and Advanced Research Center, the Thoracic Core Committee for the ECOG Cooperative Group, is the lung cancer section editor for The Oncologist journal, and is on the editorial boards of The Journal of Thoracic Oncology and Cancer Prevention Research.

Dr. David Barbie is an Associate Professor of Medicine at Harvard Medical School and Associate Director of the Belfer Center for Applied Cancer Science, as well as an Associate Member of the Broad Institute. Dr. Barbie was a Howard Hughes Medical Investigator Program Medical Student Research Fellow in Dr. Edward Harlow’s laboratory at the MGH Cancer Center, an MGH internal medicine resident and chief medical resident, and post-doctoral fellow in Dr. William Hahn’s laboratory at DFCI and the Broad Institute, where he discovered TBK1 activation in KRAS-mutant lung cancers in collaboration with colleagues across Boston, including DFCI, MGH, BWH, and MIT. Currently he is principal investigator of his own laboratory at DFCI and co-directs the Belfer Center with Dr. Pasi Jänne, while also seeing patients in the Lowe Center for Thoracic Oncology.

As a fellow he was the recipient of an ASCO Young Investigator award and NIH K08 grant. Currently he is a principal or co-principal investigator on multiple NIH grants including an R01, P01, and two U01 grants. He has also received significant funding from the V Foundation, SU2C, the Mark Foundation, the Ludwig Center, and the Parker Institute for Cancer Immunotherapy.

His laboratory has had a strong translational focus and his early collaborations with Gilead Sciences led to the first TBK1 inhibitor trials using a repurposed multitargeted JAK inhibitor. He was principal investigator of a multicenter lung cancer clinical trial using this first-generation drug and his work also led to similar studies in colorectal and pancreatic cancer which were part of the HCC SPORE in Gastrointestinal (GI) malignancies. Together with Gilead Sciences he also published one of the first potent/selective TBK1 inhibitors and demonstrated its activity in combination with PD-1 immune checkpoint blockade. More generally, this work also validated an innovative 3-dimensional microfluidic culture system using organotypic tumor spheroids, which enables ex vivo evaluation of response to cancer immunotherapies.

Dr. Barbie also has a strong track record of mentoring, an essential component of being a SPORE Director. He has successfully mentored fellows who have received internal DRP grants from the HCC Lung Cancer Program, an NIH K08 grant, Conquer Cancer Foundation award, Lung Cancer Research Foundation award, and multiple top tier Japanese Fellowship Grants. Moreover, Dr. Barbie has successfully mentored multiple fellows to start their own independent laboratories as tenure track faculty members including Dr. Russell Jenkins (MGH Cancer Center), Dr. Israel Cañadas (Fox Chase Cancer Center), and Dr. Shunsuke Kitajima (The Cancer Institute of the Japanese Foundation for Cancer). Finally, as further evidence of Dr. Sequist and Dr. Barbie’s cross-institutional collaborative relationship they have also recently co-mentored a post-doctoral fellow, Erik Knelson M.D., Ph.D, both in lung cancer clinic at MGH and in the laboratory at DFCI.

Dr. Barbie is serving as the contact PI since DFCI is the submitting institution, but both he and Dr. Sequist together will oversee all aspects of this proposal together as co-PIs, leaders of Core A, and specific Project co- leads.