The Center for Cancer Systems Pharmacology is a member of the National Cancer Institute’s Cancer Systems Biology Consortium (CSBC). The network of research centers comprising the CSBC supports basic and translational cancer research through the explicit combination of experimental biology and computational modeling, multi-dimensional data analysis, and systems engineering.
The Center for Cancer Systems Pharmacology (CCSP) is based out of the Laboratory of Systems Pharmacology (LSP) at Harvard Medical School. The CCSP focuses on constructing and validating network-level models of drug responsiveness and resistance (innate and acquired) for both immune checkpoint inhibitors (ICI) and targeted small molecule drugs in several human cancers. The CCSP aims to improve molecular understanding of oncogenic transformation leading to the initiation and progression of cancer as well the opposing immune surveillance mechanisms that keep cancers in check and presents multiple opportunities for improved therapy. The CCSP also studies the adverse effects of cancer therapies, with an initial focus on skin toxicity induced by ICIs. The over-arching goal is to reduce intrinsic and acquired resistance to drugs and to reduce adverse effects, thereby improving patient care.
Our approach involves using systems pharmacology tools and concepts to address the most significant questions encountered in the use of ICIs and targeted therapies individually and in combination in melanoma, in which both classes classes of drug can be highly effective, and in triple negative breast cancer (TNBC) and glioblastoma multiforme (GBM), in which clinical responses are sporadic. In the long-term, expected outcomes include (i) translating clinical problems in melanoma, TNBC and GBM from the bedside to bench and then back to the bedside via new drug-disease pairings, drug combinations and response biomarkers (ii) developing, validating and applying innovative pharmacological concepts to clinical trials; these concepts consider the impact of cell-to-cell variability, micro environment, and dose and drug sequencing on outcomes and (iii) reducing the burden of therapy through improved understanding of mechanism-based drug toxicities and ways of mitigating them.
The Center for Cancer Systems Pharmacology at Harvard Medical School is an NCI Cancer Systems Biology Center of Excellence funded by grant U54-CA225088 entitled “Systems Pharmacology of Therapeutic and Adverse Responses to Immune Checkpoint and Small Molecule Drugs”