Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies

Razaghi, Ali, Heimann, Kirsten, Schaeffer, Patrick M., and Gibson, Spencer B. (2018) Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies. Apoptosis, 23 (2). pp. 93-112.

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Abstract

Cancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge. Circumvention of negative regulators of cell death pathways or development of predictive and response biomarkers is, therefore, quintessential. This review critically discusses the current state of knowledge on targeting negative regulators of cell death signaling pathways including apoptosis, ferroptosis, necroptosis, autophagy, and anoikis and evaluates the recent advances in clinical and preclinical research on biomarkers of negative regulators. It aims to provide a comprehensive platform for designing efficacious polytherapies including novel agents for restoring cell death signaling pathways or targeting alternative resistance pathways to improve the chances for antitumor responses. Overall, it is concluded that nonapoptotic cell death pathways are a potential research arena for drug discovery, development of novel biomarkers and targeted therapies.

Item ID: 52353
Item Type: Article (Research - C1)
ISSN: 1573-675X
Keywords: cancer targeted therapy; drug resistance; cell death pathway; negative regulator; biomarker; immunotherapy
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Date Deposited: 29 Mar 2018 05:06
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111202 Cancer Diagnosis @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy) @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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