Apoptosis regulation and drug resistance in malignant pleural mesothelioma

Abstract

0 d ith poor prognosis and intrinsic drug resistance. aking into account a latency period of 20—50 years nd a decline in workplace exposure to asbestos in urope since the 1970s, it has been estimated that he number of men dying from MPM in Europe will ouble each year until a peak is reached in about 020 [1]. Although approximately 80% of MPMs in he Western World arise in individuals exposed o asbestos, only a fraction of those exposed to sbestos develop mesothelioma, suggesting that dditional factors play a role [2]. Although numerus single-agent and combination treatments have een examined, no effective standard treatment ith chemotherapy alone has emerged so far [3] nd the identification of more effective agents for PM remains a great challenge. Defects in apoptosis underpin both tumorigeneis and drug resistance, and investigations of the echanisms of apoptosis induction, amplification nd execution have revealed that the therapeuic efficacy of diverse anticancer agents depends Both pathways can be activated by genotoxic and metabolic stress, and result in the activation of effector caspases-3, -6 and -7 which cleave a variety of distinct substrates, resulting in nuclear fragmentation and cellular disassembly.