The biochemical and molecular mechanisms involved in the role of micro-tumor environment stress in development of drug resistance.
Biochim Biophys Acta Gen Subj. 2019 Jun 13;:
Authors: Al-Akra L, Bae DH, Leck LL, Richardson DR, Jansson PJ
BACKGROUND: Multi-drug resistance (MDR) is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Moreover, the tumor microenvironment is essential to the formation of drug resistant cancers. Recent evidence indicates that the tumor microenvironment is a critical regulator of cancer progression, distant metastasis and acquired resistance of tumors to various therapies. Despite significant advances in chemotherapy and radiotherapy, the development of therapeutic resistance leads to reduced drug efficacy.
SCOPE OF REVIEW: This review highlights mechanistic aspects of the biochemistry of the tumor microenviroment, such as the hypoglycaemia, reactive oxygen species (ROS), hypoxia and their effects in propagating MDR. This is achieved through: (A) increased survival via autophagy and failure of apoptosis; (B) altered metabolic processing; and (C) reduction in drug delivery and uptake or increased drug efflux.
MAJOR CONCLUSIONS: The development of MDR in cancer has been demonstrated to be majorly influenced by naturally occurring stressors within the tumor microenvironment, as well as chemotherapeutics. Thus, the tumor microenvironment is currently emerging as a major focus of research which needs to be carefully addressed before cancer can be successfully treated.
GENERAL SIGNIFICANCE: Elucidating the biochemical mechanisms which promote MDR is essential in development of effective therapeutics that can overcome these acquired defences in cancer cells.
PMID: 31202693 [PubMed - as supplied by publisher]