| Summary: |
Triple-negative breast cancer (TNBC) and advanced ovarian cancer are known by their poor prognosis and low survival rates. These hard-to-treat cancers display high resistance to the available therapy. Effective therapeutic options are urgently needed for these cancers.
The tumor suppressor BRCA1 has a critical role in homologous recombination (HR) DNA repair. In tumors, a functional BRCA1-mediated HR is related to therapeutic resistance, namely to platinum agents and PARP inhibitors as olaparib (approved for breast and ovarian cancer therapy). Thus, inhibition of the BRCA1-mediated HR DNA repair has emerged as an encouraging therapeutic strategy in aggressive breast and ovarian cancers.
This project provides the compound BBIT20 as the first disruptor of the BRCA1/BARD1 interaction, leading to downregulation of BRCA1 activity and subsequent HR inhibition. In vitro and in vivo pre-clinical data strongly support its advantages compared to other HR inhibitors, mainly olaparib, demonstrating its great potential as anticancer agent, either alone or in combination therapy, in the treatment of TNBC and advanced ovarian cancer. The enormous benefits that BBIT20 may bring to the personalized cancer therapy have made it worthy of the interest by the industry.
With this project, we intend to validate the antitumor activity and safety of BBIT20, in local and metastatic cancers, either alone or in combination therapy, using a patient-derived xenograft PDX) model, which is a keystone in translational cancer research, highly predicting the clinical therapeutic outcome of new drugs in patients. Importantly, due to a detailed genomic profiling of the tumor samples used in the PDX model, it is also expected to deeply characterize the genetic profile of the patients that may benefit from BBIT20 treatment. This will certainly add commercial value to BBIT20, boosting its marketing and successful clinical translation. |