Targeting autophagy in breast cancer

Abstract

Macroautophagy (referred to as autophagy here) is an intracellular degradation pathway enhanced in response to a variety of stresses and in response to nutrient deprivation. This process provides the cell with nutrients and energy by degrading aggregated and damaged proteins as well as compromised organelles. Since autophagy has been linked to diverse diseases including cancer, it has recently become a very interesting target in breast cancer treatment. Indeed, current clinical trials are trying to use chloroquine or hydroxychloroquine, alone or in combination with other drugs to inhibit autophagy during breast cancer therapy since chemotherapy and radiation, regimens that are used to treat breast cancer, are known to induce autophagy in cancer cells. Importantly, in breast cancer, autophagy has been involved in the development of resistance to chemotherapy and to anti-estrogens. Moreover, a close relationship has recently been described between autophagy and the HER2 receptor. Here, we discuss some of the recent findings relating autophagy and cancer with a particular focus on breast cancer therapy.

Keywords: Autophagy, Cancer, Breast cancer, Chemotherapy, Radiation, Estrogen receptor, HER2, Triple negative breast cancer

Core tip: Autophagy is thought to be a tumor suppressor pathway. However, once a tumor is formed, it may contribute to tumor cell survival in response to metabolic stress or to therapy. On the other hand, it has also been suggested that autophagy could be induced during breast cancer therapy to kill cells that avoid apoptosis. Here, we discuss some of the recent findings relating autophagy and cancer with a particular focus on breast cancer therapy. We conclude that there are important unresolved questions that should be addressed before autophagy can be successfully targeted for breast cancer treatment.