Breast cancer is the most common cancer in women with more than 316,000 new cases and expected 40,610 deaths in the US in 2017. Despite vast improvement in cancer management and treatment in the past years, not all subtypes of breast cancer have benefited equally. This includes the most aggressive form of invasive breast cancer, triple negative breast cancer (TNBC) subtype (ER-, PR- and HER2-), which accounts for about 20-25% of all breast cancer cases and presents a higher breast cancer-related mortality compared to other breast cancer subtypes. The poor survival rates attributed to TNBC is due to the lack of available biological targets and high rates of metastatic recurrence. Therefore, chemotherapy is the only therapeutic option for patients with metastatic TNBC. However, development of chemotherapy resistance is observed in the great majority of the cases and patients relapse within 5 years of a diagnosis. Given the unmet clinical needs, the discovery of novel therapeutic options that overcome chemoresistance of metastatic breast cancer is required. We have identified a group of genes which expression was enriched in chemotherapy resistant tumors cells, suggesting that these are potential therapeutic candidates to overcome chemotherapy resistance. Of these, CDKN1A (p21) was included. Furthermore, Immunostaining of metastatic lung tissue confirmed that surviving tumor cells under CTX treatment highly express p21. The enrichment of p21 in surviving tumor cells under chemotherapy, together with its well documented functions in cell-cycle arrest and regulation of apoptosis, provides a rationale to explore the underlying mechanisms that govern p21-induced chemoresistance and whether targeting p21 will re-sensitize the chemoresistant tumor cells in vivo.

Citation Format: Ana Rita Lourenco, Jay Lopez, Michael Crowley, Vivek Mittal, Dingcheng Gao. Awakening metastatic breast cancer cells to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2904.