Treating Drug Resistant BRCA-deficient Tumors

SLU ID #20-009 | Inhibition of PALB2 Protein for Cancer Treatment

Background

Ovarian and breast cancer represent the leading causes of cancer-related deaths world-wide and in Western nations particularly. In contrast to the significant progress in survival rates for many cancers achieved in recent years, the five year overall survival rate from ovarian cancer has remained almost unchanged since 1980. Survival of cancer cells strongly depends on efficient repair of double-stranded DNA breaks occurring during fast, uncontrolled proliferation. Breast cancer susceptibility proteins 1 and 2 (BRCA1, -2) and the partner and localizer of BRCA2 (PALB2) are key players of the most efficient homologous recombination repair of double-stranded DNA breaks and of other DNA repair pathways in dividing cells. These proteins substantially contribute to drug resistance during chemotherapy, while mutations of these proteins sensitize cancer cells to platinum-based treatment and to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). These findings have led to personalized treatment strategy of BRCA deficient cancer patients. However, there is only one FDA-approved targeted therapy available for recurrent, chemo-resistant, BRCA-proficient ovarian cancer. This lack of targeted therapies is largely because 75% of patients carry no known common germline or tumor mutations to which target therapy. Novel inhibitors have the potential to improve treatment of drug-resistant relapsed tumors, to reduce drug resistance occurrence, or provide a novel, more efficient approach to target homologous recombination and kill cancer cells.

Overview

Researchers at Saint Louis University have developed a novel PALB2 inhibitor that works to kill cancer cells by preventing the homologous recombination of double-stranded DNA breaks that occur during cell proliferation.

Benefits

The potential benefits of this technology include:

• Increasing the efficacy of treatments for drug-resistant tumors

• Increasing the efficacy of current platinum-based chemotherapy

• Minimizing drug resistance

Applications

Potential applications of this technology include:

• Treating breast cancer in BRCA deficient patients

• Treating recurrent, chemo-resistant, BRCA-proficient ovarian cancer

Opportunity

Saint Louis University is seeking partners to further develop and commercialize this technology.