Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1863, Issue 9, Pages 1390-1397Publisher
ELSEVIER
DOI: 10.1016/j.bbagen.2019.06.007
Keywords
Tumor micro-environment; Multi-drug resistance; Autophagy; Apoptosis; Metabolism; Hypoxia
Categories
Funding
- University of Sydney
- Cancer Institute of New South Wales Career Development Fellowship
- Senior Principal Research Fellowship
- National Health and Medical Research Council of Australia (NHMRC)
- National Breast Cancer Foundation (NBCF)
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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 micro-environment is essential to the formation of drug resistant cancers. Recent evidence indicates that the tumor micro-environment 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 micro-enviroment, 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 micro-environment, as well as chemotherapeutics. Thus, the tumor micro-environment 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.
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