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Leukemia Research and TreatmentVolume 2015 2015, Article ID 757694, 16 pages

Review ArticleDepartment of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605014, India

Received 26 August 2015; Revised 11 November 2015; Accepted 12 November 2015

Academic Editor: Massimo Breccia

Copyright © 2015 Kalubai Vari Khajapeer and Rajasekaran Baskaran. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic myeloid leukemia CML is a hematological malignancy that arises due to reciprocal translocation of 3′ sequences from c-Abelson ABL protooncogene of chromosome 9 with 5′ sequence of truncated break point cluster region BCR on chromosome 22. BCR-ABL is a functional oncoprotein p210 that exhibits constitutively activated tyrosine kinase causing genomic alteration of hematopoietic stem cells. BCR-ABL specific tyrosine kinase inhibitors TKIs successfully block CML progression. However, drug resistance owing to BCR-ABL mutations and overexpression is still an issue. Heat-shock proteins Hsps function as molecular chaperones facilitating proper folding of nascent polypeptides. Their increased expression under stressful conditions protects cells by stabilizing unfolded or misfolded peptides. Hsp90 is the major mammalian protein and is required by BCR-ABL for stabilization and maturation. Hsp90 inhibitors destabilize the binding of BCR-ABL protein thus leading to the formation of heteroprotein complex that is eventually degraded by the ubiquitin-proteasome pathway. Results of many novel Hsp90 inhibitors that have entered into various clinical trials are encouraging. The present review targets the current development in the CML treatment by availing Hsp90 specific inhibitors.





Autor: Kalubai Vari Khajapeer and Rajasekaran Baskaran

Fuente: https://www.hindawi.com/



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