Cancer Therapeutics Program

PROJECT SUMMARY – Cancer Therapeutics Program (CTP) The overall goal of this 25-year-old Program at the Abramson Cancer Center (ACC) is to use mechanistic insights emerging from our basic science labs and CCSG Programs to improve cancer therapy for patients with advanced solid tumors. CTP accomplishes this goal through three Specific Aims: 1) Translate mechanistic biologic insights into Phase I trials; 2) Use data from Phase I trials to perform Phase II and Phase III trials to change clinical practice; and 3) Discover and develop innovative biomarkers that enhance safety and efficacy of cancer therapies. This Program is co-led by Program Leaders (PLs) Drs. Ravi Amaravadi and Naomi Haas, both appointed in 2013. Drs. Amaravadi and Haas are NCI-funded researchers who bring highly complementary scientific visions and a notable depth of experience as accomplished translational researchers. CTP encompasses a full range of basic, translational, and clinical research. CTP works closely with leaders of the ACC Community Outreach and Engagement (COE) to understand the cancer burden in the ACC catchment area and ensure that CTP research addresses the major unmet needs in our catchment area. CTP members work on improving cancer therapies for patients with advanced, lethal and often highly symptomatic solid tumors, including lung, prostate and pancreas cancer, as well as melanoma and others. During the current funding period, the PLs aggressively recruited new junior and senior investigators to CTP, reorganized the Program into disease-focused groups, and promoted intra-Programmatic interactions through carefully selected and relevant scientific themes including autophagy, cancer cell metabolism, targeted therapies, and immunotherapy. These efforts resulted in new multi-investigator grants, including NCI Program Project grants and SPORES that include CTP members, new leadership positions in National Groups, and an increase in collaborative publications. Interventional trial accruals were more than 640 per year on average (in CTP alone), representing an increase compared to the prior funding period; 59% of interventional accruals were on investigator-initiated trials. Major accomplishments include validating autophagy as a cancer target, translating basic findings in DNA damage to new therapies in ovarian and pancreatic cancer, determining the pharmacodynamics of PD-1 therapy in patients with earlier stage melanoma, testing novel immunotherapies such as monalizumab, CD40 mAb, and CAR T cells in patients with solid tumors, and advancing circulating DNA as a biomarker of response in lung cancer. The 31 CTP full members and 28 CTP associate members represent six departments from two schools at Penn. CTP members have $14.7M in annual cancer-related research grant funding (direct costs), of which $3.1M is NCI-funded and $4.5M is peer-reviewed. This represents an increase in total funding of $8M (120% increase) since 2015. Our Program has 16 R01- equivalents. There are 540 cancer-related publications from the Program since 2015. Of these, 19% are intra- Programmatic, 38% resulted from inter-Programmatic collaborations, and 74% are multi-institutional.