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Therapeutic potential of thalidomide and its analogues in the treatment of cancer

Lookup NU author(s): Dr Gajanan Sherbet

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Abstract

Thalidomide was synthesised and launched several decades ago as a drug against respiratory infections and was administered to pregnant women for relief of morning sickness. The drug was withdrawn when its teratogenic effects came to light. Thalidomide and its analogues suppressed cell proliferation and angiogenesis and controlled invasion and metastasis of tumours in pre-clinical studies. With the recognition of its immunomodulatory and anti-inflammatory, properties, thalidomide may have found a place in the treatment of many forms of cancer and autoimmune conditions. Herein the signalling pathways modulated by thalidomides via the mediation of vascular endothelial growth factor, phosphoinositide-kinase/protein kinase B and nuclear factor kappa B, and mammalian target of rapamycin, which integrates these signalling systems, are discussed. The mode of action of thalidomides and their strategic utility in therapy are evaluated in the context of potential clinical benefits. Notwithstanding the perceived benefits, the side-effects of thalidomides need to be taken into account; they do exert teratogenic effects in animal models, although being effective at lower doses, the drugs seem to show comparatively manageable and reduced toxicity. Combination therapy of thalidomides and modulators of signaling that they influence may further reduce the severity of the side-effects by delivering inhibitory effects at reduced drug dosages. Preclinical evaluations of this kind seem warranted.


Publication metadata

Author(s): Sherbet GV

Publication type: Review

Publication status: Published

Journal: Anticancer Research

Year: 2015

Volume: 35

Issue: 11

Pages: 5767-5772

Print publication date: 01/11/2015

Acceptance date: 01/01/1900

ISSN (print): 0250-7005

ISSN (electronic): 1791-7530

Publisher: International Institute of Anticancer Research

URL: http://ar.iiarjournals.org/content/35/11/5767

PubMed id: 26503997


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