Advances in Synthetic Lethality for Personalized Cancer Treatments
A special issue of Journal of Personalized Medicine (ISSN 2075-4426).
Deadline for manuscript submissions: closed (20 August 2022) | Viewed by 7776
Special Issue Editors
Interests: stem cells; epigenetic mechanisms; noncoding RNAs; cancer stem cells
Special Issues, Collections and Topics in MDPI journals
Interests: gastric cancer; poorly cohesive carcinoma; signet ring cell; surgical oncology; minimally invasive surgery; multimodal therapies; molecular subtypes
Special Issue Information
Dear Colleagues,
The transformation from a normal cell to a cancer cell is the result of the concerted action of multilevel changes in cell organization. Despite many recent advances in precision medicine, it remains difficult to restore the activity of a damaged tumor suppressor gene, replace an inadequately expressed protein, or inhibit an oncogene in a given cancer type.
The concept of synthetic lethality describes the interaction between two genes such that one functionally buffers against mutations in the other. Targeting a protein and its function that compensate for a change in the quality or quantity of proteins gained or lost can prove fatal for a cancer cell. Synthetic lethality, exploiting the complex relationships of the cellular universe, aims to overcome the current limitations and develop personalized treatments for the benefit of patients. Any oncogenic signaling pathway and compensatory coping mechanism acting in mutant cancer cells forms the basis for the synthetic lethal strategy.
One of the most significant challenges facing the development of precision medicine is the problem of managing and understanding clinical and genomic data. The genetic concept of synthetic lethality has been applied to the DNA damage response and clinically validated through the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of tumors in individuals with loss-of-function germline mutations in BRCA1 and BRCA2 genes. Further promising strategies involve the MAT2A/PRMT5/RIOK1 axis. Exploitation of CRISPR-Cas9 and shRNA technology has revealed a large number of synthetic lethal interactions involving epigenetic-related genes, such as those encoding the SWI/SNF complex, the PRC2 complex, SETD2, KMT2C, and MLL proteins.
In the highly correlated system of the cell, many pairs of codependent functions are expected to be active as cascading consequences of genetic and epigenetic oncogenic alterations. Application of the synthetic lethality paradigm raises the possibility of precisely targeting subgroups of tumors defined by a molecular alteration.
Synthetic lethality is an engine for the discovery of anticancer drug targets. The combination of high-throughput screening with CRISPR-Cas9 and shRNA technology, omics approaches, small molecule inhibitors, and functional assays has proven to be a promising research approach. Functional genomic screening based on the genetic concept of synthetic lethality provides a way to discover drug targets in all areas of cancer cure.
We invite authors to submit experimental articles aimed at studying mechanisms and identifying strategies for developing new molecular approaches in cancer targeting which are based on synthetic lethality. Contributions can involve any molecular mechanism in the fields of genetics, epigenetics, protein function, and cell metabolism in human or nonhuman models. Findings based on bioinformatic approaches are welcome.
We also call for studies to validate combinatorial cancer treatments resulting from the synthetic lethal approach.
We accept review articles that help researchers to clarify past results and propose ideas for new approaches and strategies.
Dr. Giorgio Malpeli
Dr. Maria Bencivenga
Guest Editors
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. Journal of Personalized Medicine is an international peer-reviewed open access monthly 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 2600 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.
Keywords
- synthetic lethality
- genetic interaction
- functional genomics
- drug resistance mechanisms
- targeted therapy
- combinatorial treatment
- CRISPR/Cas9 screening
- oncogene addiction
- checkpoint inhibitor treatments
- DNA repair inhibitors