Autophagy is a homeostatic process that degrades long-lived or damaged proteins and organelles. By recycling intracellular constituents, it is buffering metabolic stress under starvation conditions. The autophagy role in cancer remains unclear and complicated as it appears to be involved in tumorigenesis, cancer development and treatment outcome in different ways. Autophagy can act as both tumor-promoting and tumor-suppressing agent depending on the stage of cancer progression. During the initiation of cancer, autophagy prevents cells from further DNA damage and genomic instability. It could also be a cell death mechanism in cancer cells with apoptotic defect. Autophagy can also promote tumor growth by facilitating oncogene-induced senescence or protecting tumors against necrosis and inflammation. Once the cancer is formed, autophagy can contribute to tumor progression (by allowing cells to survive in stressful conditions) and metastasis. There is evidence that breast cancer could also be controlled by autophagy. Regulation of this process, correlated proteins and active factors are currently under scientific study in the aspect of breast cancer effective therapeutic strategies.
Part of the book: Cell Death
A significant progress has been made in describing cellular hierarchy and the stem cell niche in the human mammary gland. Mammary stem and progenitor cells exist in two different states: epithelial-like and mesenchymal-like. Several features of the mammary stem cells predispose them to play a critical role in breast cancer initiation, progression and metastasis. Signaling pathways contributing to the self-renewal, such as Wnt, Notch, Hh and BMP, have been shown to be linked with breast cancer stem cells. Furthermore, biomarkers connected with stemness, such as CD44, CD24, EpCAM and ALDH1, have been identified and used to characterize these cells. Additionally, many different miRNA families and microenvironmental factors were shown to regulate a lot of cancer stem cells properties and maintain their stemness. All these findings have started a new era of breast cancer research. In present breast cancer, stem cells have become the targets of breast cancer therapy, although the tests are mainly on the basic stage level. Since the cancer stem cells are able to escape chemotherapy and are resistant to drugs, radiotherapy and apoptotic processes, the therapeutic targeting is mostly concentrated on the disruption of survival signaling pathways and the use of modern technology, like nanotechnology.
Part of the book: Breast Cancer