Cell Death and Survival Mechanisms in Cholangiocarcinogenesis

Cholangiocarcinoma (CCA) and other liver cancer subtypes often develop in damaged organs. Physiological agents or extrinsic factors such as toxins can induce cell death in such tissues, triggering compensatory proliferation and inflammation. Depending on extracellular and intracellular factors, different mechanisms such as apoptosis, necroptosis, ferroptosis, or autophagy can be triggered. Each of these mechanisms can lead to pro-tumorigenic or anti-tumorigenic events within a cell or through regulation of the microenvironment. However, the exact role of each cell death mechanism in CCA onset, progression, and treatment is not well known. Here, we summarize current knowledge of different cell death and survival mechanisms in patients with CCA and preclinical CCA research. We discuss cell death-related drugs with relevance to CCA treatment and how they could be used in the future to improve targeted CCA therapy.