Cell Death Pathways in Response to Antitumor Therapy

Abstract

Failure to eliminate cancer cells that have been exposed to cytotoxic agents may contribute to the development of resistance to antitumor drugs. A widespread model in present day oncology is that antitumor therapy involves the triggering of tumor cells to undergo apoptosis, and cells that can avoid apoptosis will be resistant to such therapy. Apoptosis is a defined program of cell death that is markedly influenced by the fact that many routes leading to it are mutated or deregulated in human cancer. Mutations in the tumor suppressor protein p53, a common feature of many cancers, may decrease the sensitivity of cells to some antitumor agents. Moreover, it has been increasingly reported that antitumor therapy not only causes apoptosis, but other forms of cell death as well, such as mitotic catastrophe, necrosis and autophagy, or a permanent cell arrest with phenotype characteristics of senescence. Mitotic catastrophe is a form of cell death that results from abnormal mitosis, which does not seem to depend on wild-type p53. Sometimes mitotic catastrophe is used restrictively for faulty mitosis leading to cell death, which may occur via apoptosis or necrosis. We critically review herein how antitumor therapy may elicit the response of human cancers through different cell pathways leading to cell death.

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

“…Mitotic catastrophe is an abnormal mitosis that is characterized by micronucleated cells that continue with mitosis to form aneuploid cells, abort mitosis and die apoptotic or necrotic deaths, or undergo irreversible growth arrest. Thus, the term mitotic catastrophe should be restricted to faulty mitosis leading to irreversible growth arrest or cell death (by apoptosis or necrosis) (Vakifahmetoglu et al, 2008b;Kroemer et al, 2009;Portugal et al, 2009Portugal et al, , 2010.…”

Zoledronic acid reverses cisplatin resistance in nasopharyngeal carcinoma cells by activating the mitochondrial apoptotic pathway

“…To prevent drug resistance and recurrence, chemotherapeutic regimes must effectively induce the apoptosis of cancer cells. Although some patients initially respond to chemotherapy, the majority of patients with advanced tumors experience treatment failure, as NPC cells often acquire resistance to drugs and may develop multidrug resistance (4)(5)(6)(7)(8).…”

“…Cisplatin (CDDP), which is a chemotherapeutic agent that is able to induce dsDNA breaks, is one of the most active drugs for the treatment of NPC (4)(5)(6)(7)(8). Notably, radiotherapy and adjuvant CDDP chemotherapy have emerged as the standard therapeutic strategy for NPC (11,12).…”

Autophagy as a mediator of chemotherapy-induced cell death in cancer

“…Accumulating evidence now shows that anticancer agents also elicit other forms of nonapoptotic cell death including necrosis, mitotic catastrophe, autophagy and senescence [4][5][6].…”