OPA1 a new mitochondrial target in cancer therapy

摘要

Cancer is one of the most prevalent diseases of the ageing western world population. It is now accepted that cancer is a complex disease resulting from the interplay between the tumor cell and its microenvironment. Cancer cells are highly proliferative, are protected from apoptosis and from the immune system and can transform their microenvironment. A key facet of cancer is the activation of quiescent blood vessels to induce neovascularization, to support tumor growth and metastasis dissemination [1]. Angiogenesis, the new blood vessel formation from preexisting one, is not only crucial for cancer, but also for embryogenesis, tissue repair and ovulation and is associated to inflammation and diabetic retinopathy. One of the yet unmet needs in anticancer therapy is how to abrogate its metastatization, often the primary cause of death for most parenchymatous tumors [2]. In this respect, antiangiogenic therapy that starves the tumor bulk from oxygen and nutrients and reduces the conduits for cancer cell dissemination outside of the primary tumor location is a widely explored avenue. Classically, antiangiogenic therapies inhibit Vascular Endothelial Growth Factor (VEGF), the main driver of angiogenesis. They comprise antagonist monoclonal antibodies like Bevacizumab, FDA/EMA approved for colon, lung, renal and breast cancer; or small molecules inhibitors of VEGF receptor tyrosine kinase activity like lapatinib, sunitinib, sorafenib, axitinib, and pazopanib, approved for breast, renal, soft tissues, hepatocellular and rarer cancers [3]. However, as these therapies are being used in the clinics, oncologists are confronted with the emergence of resistance, calling for the identification of new antiangiogenic therapies that do not directly target the VEGF pathway.