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Special Issue "Genomic Instability and How to Exploit It for Cancer Cell Vulnerability"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (22 September 2022) | Viewed by 650

Special Issue Editor

Dr. Samirkumar B. Amin
E-Mail Website
Guest Editor
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Interests: cancer evolution; comparative genomics; glioma; aneuploidy; oncogenesis

Special Issue Information

Dear Colleagues,

In this Special Issue, we invite manuscripts that focus on the role of genomic instability in cancer evolution and how it can be leveraged to exploit cancer cell vulnerabilities.

Genomic instability is a major source of both variation required for the clonal evolution of cancer and the resulting intratumoral heterogeneity (ITH). This in turn drives tumor growth and acts as a significant barrier to effective cancer therapies. Genomic instability predominantly stems from the process known as chromosomal instability (CIN), which is characterized by a high rate of chromosomal mis-segregation. This results in numerical CIN (i.e., a change in the numbers of whole chromosomes (aneuploidy) or arms) and structural CIN, leading to pervasive somatic copy-number aberrations (SCNAs). Together, SCNAs and aneuploidies cover nearly 25% of the genome across more than 90% of solid tumors. Such extensive damage to genomic structural integrity is detrimental to otherwise normal cells. However, cancer cells evolve to tolerate and, in fact, accumulate more alterations over the natural history of tumor evolution by selecting for fitness-promoting (oncogenic) regions and discarding (negative selection) fitness-reducing (tumor suppressors) regions and loss regions with TSGs. Nonetheless, cancer cells must also overcome resulting cellular stress responses that guard cells against insult from progressive CIN. Experimental and pan-cancer genomic profiling results suggest that cancer cells adapt to such stress by preserving essential genes in loss-of-heterozygosity (LOH) regions and further by whole-genome duplications following LOH events. Importantly, such regions can be further be exploited to identify cancer cell vulnerability (e.g., to sensitize cancer cells that would otherwise be resistant to apoptosis, senescence, or both). Besides CIN, other mechanisms like microsatellite instability (MSI) and inherited syndromes related to DNA damage and repair processes (e.g., hereditary MYH-associated polyposis) also add to increased somatic mutational burden and fuel cancer growth.

Here, we invite original research articles and reviews related to some of the prevailing questions regarding genomic instability in cancer: How do cancer cells develop tolerance to damage insinuated by progressive instability? Which genes and regulatory regions within SCNAs and aneuploidies enable this tolerance and promote cancer cell fitness? Which stress-response barriers in the natural history of tumor evolution cancer cells must overcome by selecting for fitness-promoting SCNAs and aneuploid regions? Which structural alterations are a result of selective pressures induced by either the tumor immune microenvironment or cancer therapies (i.e., to identify the SCNAs driving recurrent or treatment-resistant metastatic cancers)?

Dr. Samirkumar Amin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • genomic instability
  • clonal evolution
  • aneuploidy
  • stress response
  • immune microenvironment
  • cancer therapies

Published Papers (1 paper)

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Pre-Existing and Acquired Resistance to PARP Inhibitor-Induced Synthetic Lethality
Cancers 2022, 14(23), 5795; https://doi.org/10.3390/cancers14235795 - 24 Nov 2022
Viewed by 397
The advanced development of synthetic lethality has opened the doors for specific anti-cancer medications of personalized medicine and efficient therapies against cancers. One of the most popular approaches being investigated is targeting DNA repair pathways as the implementation of the PARP inhibitor (PARPi) [...] Read more.
The advanced development of synthetic lethality has opened the doors for specific anti-cancer medications of personalized medicine and efficient therapies against cancers. One of the most popular approaches being investigated is targeting DNA repair pathways as the implementation of the PARP inhibitor (PARPi) into individual or combinational therapeutic schemes. Such treatment has been effectively employed against homologous recombination-defective solid tumors as well as hematopoietic malignancies. However, the resistance to PARPi has been observed in both preclinical research and clinical treatment. Therefore, elucidating the mechanisms responsible for the resistance to PARPi is pivotal for the further success of this intervention. Apart from mechanisms of acquired resistance, the bone marrow microenvironment provides a pre-existing mechanism to induce the inefficiency of PARPi in leukemic cells. Here, we describe the pre-existing and acquired mechanisms of the resistance to PARPi-induced synthetic lethality. We also discuss the potential rationales for developing effective therapies to prevent/repress the PARPi resistance in cancer cells. Full article
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