Although breast cancer incidence has increased and is forecast to continue to rise, due to early detection and improved treatments there has been a steady decrease in overall mortality rates in women diagnosed with breast cancer. However, although the survival rates for women with early stage breast cancer has greatly improved over the past 30 years, the survival rates of patients who are diagnosed with metastases has not greatly changed. Currently treatment options for these patients are limited and the need to identify fundamental molecular mechanisms of metastasis, towards which more effective treatments can be targeted, is currently needed.
One such mechanism is macro autophagy (here after referred to as autophagy), a process whereby long-lived cellular proteins are degraded to maintain amino acid pools and metabolic substrates under stressed cellular conditions, which has been shown to both protect and promote the cancer phenotype. Currently, the exact molecular mechanisms and regulators that are associated with autophagic activity that it either promotes or inhibits cancer survival and progression are yet to be clearly defined.
Recently, we examined the genetic landscape of human mammary epithelial cells transformed with oncogenic H-RAS and identified the upregulation of multiple key autophagic molecules.
In a panel of breast cancer cells, we observed autophagic activity at increasingly high basal levels that associated with a more advanced/aggressive breast cancer cell phenotype. Inhibition of autophagic activity through a number of pharmacological agents proved cytotoxic in a number of breast cancer cell line models but not in non-transformed breast epithelial cells, highlighting the necessity and increasing requirement of this pathway in transformed and highly advanced cancer cell phenotypes.
Identification of the sensitivity of advanced cancer cells to autophagy inhibition, highlights a promising adjuvant treatment strategy for targeting metastatic disease.