Cancer Drug Discovery
Despite major advances in cancer treatment, drug resistance and disease recurrence remain significant challenges. Tumors that initially respond to therapy can develop resistance, limiting the durability of treatment and creating an urgent need for new therapeutic strategies. The Sacchettini lab is focused on discovering and advancing small molecules that can overcome drug resistance, enhance the activity of existing therapies, and provide new approaches for the treatment and prevention of cancer.
Our cancer drug discovery program combines high-throughput screening, medicinal chemistry, structural biology, mechanism-of-action studies, and in-vivo validation to identify promising compounds and understand how they affect cancer cells. Our work has particularly focused on prostate, lymphomas and ovarian cancer.
Overcoming Drug Resistance in Cancer
Through studies of drug combinations and chemical compound libraries, we have identified compounds that enhance the activity of commonly used cancer therapies and can restore drug sensitivity in resistant cancer cells. Our studies identified a series of compounds in the ansamycin class of antibiotics that synergize with multiple commonly administered cancer drugs, potentially allowing effective treatment at lower drug doses (Sacchettini et al. 2017; US Patents 9,539,237B2 and 9,867,807B2).
Our cancer drug discovery program combines high-throughput screening, medicinal chemistry, structural biology, mechanism-of-action studies, and in-vivo validation to identify promising compounds and understand how they affect cancer cells. Our work has particularly focused on prostate, lymphomas and ovarian cancer.
Prostate Cancer Drug Discovery
We are expanding our cancer drug discovery efforts to prostate cancer through a collaboration with Dr. Chendil Damodaran in the Texas A&M School of Pharmacy. Our collaborative studies combine drug discovery and mechanistic approaches with prostate cancer biology to identify compounds with potential therapeutic activity.
Promising compounds are being evaluated in mouse models of prostate cancer to determine their effects on tumor growth and progression and to establish their potential for further development. These studies provide a pathway from the identification of active compounds through mechanistic studies and preclinical validation.
Natural Products for Cancer Interception and Prevention
Our newest cancer research program focuses on the discovery of natural products for the chemoprevention of advanced prostate cancer. Through a new grant supported by the National Cancer Institute’s Discovery and Development of Natural Products for Cancer Interception and Prevention (DDNP-CIP) program, we are collaborating with Dr. Damodaran to identify natural products with potential to prevent or intercept the progression of prostate cancer.
Natural products represent a vast and chemically diverse source of biologically active molecules. We are applying modern high-throughput screening, biochemical assays, structural biology, and drug-discovery approaches to systematically identify and characterize natural products with activity against prostate cancer. Candidate compounds will be investigated to understand their mechanisms of action and evaluated for their potential to prevent or slow cancer progression.
This program builds on our expertise in structure-guided drug discovery and screening while opening a new avenue for identifying compounds that may not only treat established disease, but also intercept the biological processes that drive cancer progression.