Chemotherapy, Tumor Microenvironment, and Apoptosis

Minimally transformed cells are more apoptotically sensitive than their untransformed wild-type counterparts to apoptosis induced by chemotherapeutic compounds, or by the microenvironmental stresses of the tumor, such as hypoxia. However, most solid-tumor cells have acquired additional genetic alterations that reduce their sensitivity to chemotherapy- and hypoxia-induced apoptosis. One question that has not been explored is how the hypoxic microenvironment of tumors affects the apoptotic response of tumor cells to chemotherapy during treatment. Although it is widely accepted that the decreased proliferative capacity of hypoxic tumor cells makes them more refractory to killing by chemotherapeutic agents that require cell proliferation to be effective, agents now exist that are able to induce apoptosis under growth-inhibiting hypoxic conditions. In addition, new strategies to make tumors more oxic, by inducing apoptosis, should also improve tumor response to chemotherapy. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.