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The Role of Cancer Stem Cells in Anticancer Therapy Resistance

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 4031

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Guest Editor
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, 22381 Lund, Sweden
Interests: anticancer drugs resistance; drug repurposing; molecular targeted therapy; predictive markers; receptor tyrosine kinase biology; cellular signaling
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Special Issue Information

Dear Colleagues,

A Special Issue on the topic "The Role of Cancer Stem Cells in Anticancer Therapy Resistance" is being prepared for the journal IJMS. Despite incredible progress in cancer treatment, the cure rate remains quite low due to the fact that almost all cancer patients develop resistance to anticancer therapies. Cancer treatment elicits specific genetic and epigenetic changes in cancer cells and in the microenvironment in which cancer cells reside, contributing to resistance. Accumulating pieces of evidence suggest that a small subpopulation of cancer cells known as cancer stem cells derive therapy resistance and, thus, cancer relapse. The field is moving forward rapidly, and gaining a better understanding of the features of cancer stem cells is important to establish the foundation of efficient new cancer treatments.

Original manuscripts and reviews dealing with therapy resistance issues in cancer and focusing on cancer stem cells are very welcome from experts in the field.

Dr. Julhash U. Kazi
Guest Editor

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Keywords

  • drug resistance
  • anticancer therapy
  • cancer stem cells
  • targeted therapy

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Published Papers (1 paper)

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Research

12 pages, 3618 KiB  
Article
Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling
by Kinjal Shah, Lina Al Ashiri, Ahmad Nasimian, Mehreen Ahmed and Julhash U. Kazi
Int. J. Mol. Sci. 2023, 24(5), 5004; https://doi.org/10.3390/ijms24055004 - 5 Mar 2023
Cited by 7 | Viewed by 3475
Abstract
Therapy resistance remains one of the major challenges for cancer treatment that largely limits treatment benefits and patient survival. The underlying mechanisms that lead to therapy resistance are highly complicated because of the specificity to the cancer subtype and therapy. The expression of [...] Read more.
Therapy resistance remains one of the major challenges for cancer treatment that largely limits treatment benefits and patient survival. The underlying mechanisms that lead to therapy resistance are highly complicated because of the specificity to the cancer subtype and therapy. The expression of the anti-apoptotic protein BCL2 has been shown to be deregulated in T-cell acute lymphoblastic leukemia (T-ALL), where different T-ALL cells display a differential response to the BCL2-specific inhibitor venetoclax. In this study, we observed that the expression of anti-apoptotic BCL2 family genes, such as BCL2, BCL2L1, and MCL1, is highly varied in T-ALL patients, and inhibitors targeting proteins coded by these genes display differential responses in T-ALL cell lines. Three T-ALL cell lines (ALL-SIL, MOLT-16, and LOUCY) were highly sensitive to BCL2 inhibition within a panel of cell lines tested. These cell lines displayed differential BCL2 and BCL2L1 expression. Prolonged exposure to venetoclax led to the development of resistance to it in all three sensitive cell lines. To understand how cells developed venetoclax resistance, we monitored the expression of BCL2, BCL2L1, and MCL1 over the treatment period and compared gene expression between resistant cells and parental sensitive cells. We observed a different trend of regulation in terms of BCL2 family gene expression and global gene expression profile including genes reported to be expressed in cancer stem cells. Gene set enrichment analysis (GSEA) showed enrichment of cytokine signaling in all three cell lines which was supported by the phospho-kinase array where STAT5 phosphorylation was found to be elevated in resistant cells. Collectively, our data suggest that venetoclax resistance can be mediated through the enrichment of distinct gene signatures and cytokine signaling pathways. Full article
(This article belongs to the Special Issue The Role of Cancer Stem Cells in Anticancer Therapy Resistance)
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