Pivotal role of cancer stemness in TNBC PDX model

Triple-negative breast cancer (TNBC) is a highly metastatic subtype that lacks hormone receptors and HER2 expression, making it unresponsive to conventional hormonal therapies. Late diagnosis of TNBC limits treatment options to surgery and chemotherapy. Cancer stemness is a major factor in tumor growth, promoting cancer proliferation and aiding in the metastasis of cancer cells to other organs. In this study, we are investigating the cancer stemness marker CD44 in two different conditions: normoxia and hypoxia. Hypoxia promotes the growth of cancer stemness. To verify this, we used MDA-MB 231 and TNBC PDX cells. Interestingly, we found that the expression of CD44 is significantly higher in the hypoxic condition compared to normoxia. To validate this, we also checked the expression in 3D cell cultures (spheroids) and TNBC PDX tumors. For future studies we are planning for the treatment with anticancer drug doxorubicin and a Stat 3 inhibitor napabucasin. Our hypothesis is that the combination of these drugs will downregulate cancer stemness, leading to the killing of cancer cells and reduction of tumor metastasis.