Strategic therapeutic approaches to overcome emerging dual SRC/ABL kinase inhibitors resistances in chronic phase Ph positive chronic myeloid leukemia

Authors

  • Rajat Rana R.M Medical College, Annamalai University
  • Soumadip Das R.M Medical College, Annamalai University
  • Aravinda Swami R.M Medical College & Hospital, Annamalai University, India
  • Doreen Pon Assistant Professor, Pharm.D, BCOP, Pharmacy Practice and Administration, College of Pharmacy, Western University, California
  • S Ramesh R.M Medical College & Hospital, Annamalai University
  • Sappa Dilip Kumar R.M Medical College & Hospital, Annamalai University

DOI:

https://doi.org/10.3126/ajms.v6i1.10454

Keywords:

Chronic myeloid leukemia, Resistances, BCR-ABL, tyrosine kinase inhibitor, mutation

Abstract

Chronic myeloid leukemia (CML) is a haematopoietic neoplasm with clinically distinct phases and BCR⁄ABL1 oncogene. Imatinib mesylate, a potent inhibitor of BCR-ABL was highly effective in CML but later in-vitro derived cell line with resistance namely BCR-ABL duplication point mutation, P loop mutation, T315I mutation, C helix, SH2 domain, activation loop, C terminal lobe, SRC family kinase activation led to development of Nilotinib. Although it has potential drug targets as BCR-ABL kinase, KIT, PDGFR but has no role in overcoming in Src family kinase. It prompted strategic rational drug design of Dual Src Family Kinase/Abl Inhibitor Dasatinib, active against 15 clinically significant Imatinib resistant BCR-ABL mutations but inactive against T315I mutation. The propensity of Ph+ CML to develop novel mechanism of resistance led designing of rational therapeutic approaches to eradicate minutest residual diseases along with long term resistance risk.

DOI: http://dx.doi.org/10.3126/ajms.v6i1.10454

Asian Journal of Medical Sciences Vol.6(1) 2015 8-15

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Author Biographies

Rajat Rana, R.M Medical College, Annamalai University

Doctor of Pharmacy

Soumadip Das, R.M Medical College, Annamalai University

Doctor of Pharmacy

Aravinda Swami, R.M Medical College & Hospital, Annamalai University, India

Doctor of Pharmacy

Doreen Pon, Assistant Professor, Pharm.D, BCOP, Pharmacy Practice and Administration, College of Pharmacy, Western University, California

Assistant Professor, Pharm.D, BCOP, Pharmacy Practice and Administration, College of Pharmacy, Western University, 

S Ramesh, R.M Medical College & Hospital, Annamalai University

Professor, M.D,

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Published

2014-07-24

How to Cite

Rana, R., Das, S., Swami, A., Pon, D., Ramesh, S., & Kumar, S. D. (2014). Strategic therapeutic approaches to overcome emerging dual SRC/ABL kinase inhibitors resistances in chronic phase Ph positive chronic myeloid leukemia. Asian Journal of Medical Sciences, 6(1), 8–15. https://doi.org/10.3126/ajms.v6i1.10454

Issue

Section

Review Articles