RHAMM as a biomarker and therapeutic target in triple-negative breast cancer
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterized by early metastases and poor prognosis. Discovering novel biomarkers and therapeutic targets is necessary to improve TNBC patient outcomes as resistance to chemotherapy, the main therapeutic approach for TNBC, is common. In my study, RHAMM promoted proliferation of TNBC MDA-MB-231 tumour cells. RHAMM expression increased sensitivity to doxorubicin (p=0.0002) and strongly increased sensitivity to the FDA-approved MEK1/2 inhibitor trametinib (p≤0.0001). Doxorubicin and trametinib selectively killed RHAMM+/+ MDA-MB-231 tumour cells grown as co-cultures with RHAMM-/- MDA-MB-231 tumour cells. RHAMM-loss or trametinib decreased phosphorylated ERK1/2 protein levels and promoted apoptosis through cell surface RHAMM/HA interactions. The combination of paclitaxel, a chemotherapeutic, and trametinib synergistically promoted apoptosis of the RHAMM+/+ MDA-MB-231 tumour cells. Therefore, RHAMM is a candidate novel biomarker in TNBC, and its expression can be exploited for targeted therapy, which has potential clinical utility for the management of TNBC.