Breast cancer is the most common cancer in women, with roughly 15-20% of new cases classified as triple-negative breast cancer (TNBC), which is the most aggressive subtype. Traditional chemotherapy and radiation are very toxic to both cancer and normal cells resulting in severe side effects. As a result, it is vital to discover new anti-cancer compounds targeting TNBC while causing minimum damage to normal tissues. ROR1 (Receptor tyrosine kinase-like Orphan Receptor 1) is an oncofetal protein overexpressed in numerous human cancers including TNBC but not in normal adult tissues. Dr. Peethambaran’s work aims to find potential small molecules targeting ROR1 using an in-silico approach and validate the candidates using in vitro approaches on TNBC cell lines. Our collaborator has expertise in GROMACS 2020.4 on the BRAF server of CDAC to perform MD simulations which allowed for rigorous procedures to predict compounds with high affinity for ROR1. We are now in the process of validating the top 10 compounds on the list using in vitro assays to test the potency of the compounds. We demonstrated that one of the compounds can kill TNBC at a very low dose, inhibit proliferation, and induce apoptosis but with the least harm to non-malignant breast cells. The study was published in the Frontiers in Cell and Developmental Biology, 2023, which is a high-impact journal with wide scientific outreach. We are currently validating other compounds for their efficacy in killing TNBC cells. Additionally, the findings would serve as proof-of-concept for testing in other ROR1-upregulated malignancies.
Dr. Bela Peethambaran, PhD’s work aims to find potential small molecules targeting ROR1 using an in-silico approach and validate the candidates using in vitro approaches on TNBC cell lines. W. W. Smith Charitable Trust Research Project: “Identification and validation of small molecules targeting tyrosine kinase-like orphan receptors for anti-cancer therapy against triple-negative breast cancer”