Page 59 - JCTR-9-6

Journal of Clinical and Translational Research 2023; 9(6): 423-432

Journal of Clinical and Translational Research

Journal homepage: http://www.jctres.com/en/home

REVIEW ARTICLE

A possible novel therapeutic targets of selinexor in acute lymphoblastic

leukemia: a comprehensive review

Pushkar Malakar *, Nitin Sagar , Bandana Chakravarti , Didhiti Singha , Meghna Mondal , Rajesh Kumar Kar 4
1
1
3
1
2
1 Department of Biomedical Science and Technology, School of Biological Sciences, Ramakrishna Mission Vivekananda Educational and Research
Institute (RKMVERI), Kolkata, West Bengal, India, Stem Cell Research Centre, Department of Hematology, Sanjay Gandhi Postgraduate Institute
2
of Medical Sciences, Lucknow, Uttar Pradesh, India, Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences,
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Lucknow, Uttar Pradesh, India, Department of Neurosurgery, School of Medicine, Yale University, New Haven, Connecticut, United States of America
4
ARTICLE INFO ABSTRACT
Article history: Background and Aim: Acute lymphoblastic leukemia (ALL) presents a formidable challenge
Received: July 08, 2023 in pediatric and adolescent healthcare due to its aggressive nature and high relapse rates. Despite
Revised: August 26, 2023 therapeutic advancements, the demand for more effective treatments remains pressing. In the realm of
Accepted: September 18, 2023 hematologic malignancies, selective inhibitors of nuclear export (SINE) have emerged as promising
Published online: November 22, 2023 agents, particularly in evading resistance observed with conventional chemotherapy in acute myeloid
leukemia (AML). Selinexor, a prominent SINE compound, has exhibited promising anti-leukemic
Keywords: effects in murine models of AML, laying the foundation for its clinical evaluation. Furthermore,
Selinexor selinexor has been utilized in clinical trials both as a single-agent therapy and in combination with
Acute lymphoblastic leukemia established regimens for a wide range of solid and liquid tumors. However, the precise impact of
Mammalian target of rapamycin signaling selinexor in the context of ALL, specifically as a single agent or in combination therapies, remains
Cancer glucose metabolism unexplored. Unraveling the mechanistic intricacies underlying selinexor’s actions in ALL holds the
Alternative splicing key to optimizing its efficacy either as a monotherapy or in combination therapies. Notably, within
Long noncoding RNAs the intricate landscape of ALL pathogenesis, critical factors including the mammalian target of
Autophagy rapamycin signaling cascade, aberrations in cancer glucose metabolism, occurrences of alternative
splicing, perturbed expressions of dysregulated long noncoding RNAs, and impaired autophagic
*Corresponding author: processes have emerged as pivotal determinants. This comprehensive review undertakes a systematic
Pushkar Malakar exploration of potential therapeutic targets that hold the promise of augmenting selinexor’s efficacy
Department of Biomedical Science and within the unique landscape of ALL.
Technology, School of Biological Sciences, Relevance for Patients: This study highlights the possible therapeutic targets of selinexor in
Ramakrishna Mission Vivekananda Educational ALL. Understanding the intricate molecular mechanisms, the rational refinement of selinexor’s
and Research Institute (RKMVERI), administration, both as a single agent and as a synergistic component in combination therapies could
Kolkata, India. lead to new avenues for improving the treatment outcomes in ALL patients.
Email: pushkarbt@gm.rkmvu.ac.in
© 2023 Author(s). This is an Open-Access
article distributed under the terms of the 1. Introduction
Creative Commons Attribution-Noncommercial
License, permitting all non-commercial use, Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) represent two
distribution, and reproduction in any medium, distinct forms of acute leukemia, which are fast-growing blood cancers that originate in the
provided the original work is properly cited.
bone marrow and affect the white blood cells [1,2]. However, they differ in terms of the
specific types of white blood cells they affect, their prevalence across various age groups,
treatment strategies, and certain genetic and clinical attributes. AML primarily affects
myeloid cells, responsible for producing various types of mature blood cells including red
blood cells, platelets, and certain white blood cell varieties [3]. AML is linked to several
genetic mutations (FLT3, NPM1, and IDH1/IDH2 mutations) that can impact treatment

DOI: http://dx.doi.org/10.18053/jctres.09.202306.23-00088