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Imatinib Analogs in Chronic Myeloid Leukemia: a Systematic Qualitative Review

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Abstract

Purpose of Review

The development of the Philadelphia chromosome characterizes chronic myeloid leukemia (CML) and the subsequent oncogenesis of fusion protein BCR-ABL activation. Our improved awareness of the molecular underpinnings of CML has enabled the creation of exceptionally potent targeted medications that prevent the action of BCR-ABL tyrosine kinase. Imatinib (1st TKIs) was developed with the intention of treating chronic myeloid leukemia (CML) at the molecular level. It continues to be the most prevalent frequently used for CML therapy and is currently also approved for a number of additional malignancies caused by BCR-ABL, c-KIT, and PDGFR. Imatinib is 95% bound to plasma proteins, is taken orally, is primarily hepatically removed with an inadequate liver clearance proportion, and acts intracellularly. Patients, however, may experience imatinib resistance, which is frequently brought on by BCR-ABL mutations. Adverse reactions in imatinib-treated patients have shown to be manageable across a spectrum of severity with timely and adequate care and very seldom necessitate a permanent cessation of medication. A number of small agents, notably dasatinib, imatinib, nilotinib, bosutinib, and ponatinib, asciminib, and olverembatinib, are employed to treat CML. Some novel strategies adopted for CML made this manuscript valuable for readers.

Recent Findings

Evidence suggests the purpose of imatinib analogs (TKIs) in treatment for chronic myeloid leukemia. Still, there is recent development in chronic myeloid leukemia therapy due to emergence of resistance.

Summary

This review paper emphasizes 1st-generation, 2nd-generation, 3rd-generation, 4th-generation TKIs, their limitations, success, and some future possible strategies to eradicate future Ph + CML cells from a biological perspective.

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Abbreviations

IM:

Imatinib

CML:

Chronic myeloid leukemia

ABL:

Abelson murine leukemia

BCR:

Breakpoint cluster region

TKI:

Tyrosine kinase inhibitor

GISTs:

Gastrointestinal stromal tumors

MMR:

Major molecular response

CCyR:

Complete cytogenetic response

OS:

Overall survival

AAG:

Alpha-1-acid glycoprotein

NDIM:

N-desmethyl imatinib

BP:

Blast phase

AP:

Accelerated phase

CP:

Chronic phase

PFS:

Progression-free survival

VEGFR:

Vascular endothelial growth factor receptor

OD:

Once daily

BID:

Twice daily

SEER:

Surveillance, epidemiology, and end results

IRIS:

International Randomized Study

STI:

Signal transduction inhibitor

CHR:

Complete hematological response

PDGFR:

Platelet-derived growth factor receptor

SCT:

Stem cell transplantation

TFR:

Treatment-free remission

TOPS:

Tyrosine kinase inhibitor optimization and selectivity

MDACC:

The MD Anderson Cancer Center

NK:

Natural killer

Treg:

The frequency of regulatory T lymphocytes

DMR:

Deep molecular response

M-MDSC:

Monocyte subset of myeloid-derived suppressor cells

NCCN:

Comprehensive cancer network

ELN:

European leukemia network

EGFR:

Estimated glomerular filtration rate

ALT:

Alanine aminotransaminase

AST:

Alanine aminotransferase

RCT:

Randomized controlled trial

AE:

Adverse event

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Authors and Affiliations

  1. Department of Pharmacy, Panipat Institute of Engineering & Technology (PIET) Samalkha, Panipat, Haryana-132102, India

    Kavita Sangwan & Suman Khurana

  2. Department of Pharmacy, School of Medical & Allied Sciences, GD Goenka University, Gurgaon-122103, India

    Pratibha Dhakla

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  1. Kavita Sangwan
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  2. Suman Khurana
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  3. Pratibha Dhakla
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Correspondence to Pratibha Dhakla.

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Sangwan, K., Khurana, S. & Dhakla, P. Imatinib Analogs in Chronic Myeloid Leukemia: a Systematic Qualitative Review. Curr Pharmacol Rep 9, 99–116 (2023). https://doi.org/10.1007/s40495-023-00316-0

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