ReviewClinical cancer research : an official journal of the American Association for Cancer Research2015
RAS Synthetic Lethal Screens Revisited: Still Seeking the Elusive Prize?
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 165 citations in OpenAlex.
- Toxoplasma gondii infection reduces CD59 expression through downregulation of JAK2/STAT3 signaling axis to enhance decidual NK cell cytotoxicity via the RAS/MAPK pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Review
- Macrophage-Derived PDGF-BB and GDF-15 Promote Drug Resistance in KRAS-Mutant Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Spliceosome induction is a druggable dependency of RAS-driven senescence and cancer.Nature communications · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- CDCP1-targeting ADC outperforms standard therapies in Ras-mutant pancreatic cancer.Molecular therapy. Oncology · 2025Article
- Review
- Potential promising of synthetic lethality in cancer research and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- The pro-oncogenic noncanonical activity of a RAS•GTP:RanGAP1 complex facilitates nuclear protein export.Nature cancer · 2024Article
- MPASL: multi-perspective learning knowledge graph attention network for synthetic lethality prediction in human cancer.Frontiers in pharmacology · 2024Article
- Complex synthetic lethality in cancer.Nature genetics · 2023Review
- Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress.Nature communications · 2023Article
- Plasma cell myeloma with RAS/BRAF mutations is frequently associated with a complex karyotype, advanced stage disease, and poorer prognosis.Cancer medicine · 2023Article
- Covalent inhibitor targets KRasGenes & diseases · 2023Review
- Exploiting Cancer Synthetic Lethality in Cancer-Lessons Learnt from PARP Inhibitors.Cancer treatment and research · 2023Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
1 author at 1 institution in 2 countries.
Funding
Abstract
The RAS genes are critical oncogenic drivers activated by point mutation in some 20% of human malignancies. However, no pharmacologic approaches to targeting RAS proteins directly have yet succeeded, leading to suggestions that these proteins may be "undruggable." This has led to two alternative indirect approaches to targeting RAS function in cancer. One has been to target RAS signaling pathways downstream at tractable enzymes such as kinases, particularly in combination. The other, which is the focus of this review, has been to seek targets that are essential in cells bearing an activated RAS oncogene, but not those without. This synthetic lethal approach, while rooted in ideas from invertebrate genetics, has been inspired most strongly by the successful use of PARP inhibitors, such as olaparib, in the clinic to treat BRCA defective cancers. Several large-scale screens have been carried out using RNA interference-mediated expression silencing to find genes that are uniquely essential to RAS-mutant but not wild-type cells. These screens have been notable for the low degree of overlap between their results, with the possible exception of proteasome components, and have yet to lead to successful new clinical approaches to the treatment of RAS-mutant cancers. Possible reasons for these disappointing results are discussed here, along with a reevaluation of the approaches taken. On the basis of experience to date, RAS synthetic lethality has so far fallen some way short of its original promise and remains unproven as an approach to finding effective new ways of tackling RAS-mutant cancers. Clin Cancer Res; 21(8); 1802-9. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers."
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.