Therapeutic potency of heat-shock protein-90 pharmacological inhibitors in the treatment of gastrointestinal cancer, current status and perspectives

Author:

Boroumand Nadia1,Saghi Hossein1,Avan Amir23,Bahreyni Amirhossein4,Ryzhikov Mikhail5,Khazaei Majid6,Hassanian Seyed Mahdi127ORCID

Affiliation:

1. Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3. Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4. Department of Clinical Biochemistry and Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran

5. Division of Pulmonary and Critical Care Medicine, Washington University, School of Medicine, Saint Louis, MO, USA

6. Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7. Microanatomy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Abstract Objectives Heat-shock protein-90 (HSP90) chaperone machinery is critical to the folding, stability and activity of several client proteins including many responsible for tumour initiation, progression and metastasis. Overexpression of HSP90 is correlated with poor prognosis of GI cancer. Key findings Pharmacological inhibitors of HSP90 suppress tumorigenic effects of HSP90 by suppressing angiogenesis, survival, metastasis and drug resistance in GI cancer. This review summarizes the role of HSP90 inhibitors in the treatment of GI cancer. Summary We have presented different antitumour mechanisms of HSP90 inhibitors in cancer treatment. Suppression of HSP90 signalling via specific and novel pharmacological inhibitors is a potentially novel therapeutic approach for patients with GI cancer for a better understanding and hence a better management of this disease.

Funder

Mashhad University of Medical Sciences

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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