ArticleCancer cell2013
Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models.
Article in Cancer cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
239 citing papers in PubMed, 1 synthesis or guideline pooled it, 378 citations in OpenAlex.
- The safety and efficacy of binimetinib for lung cancer: a systematic review.BMC pulmonary medicine · 2024Pooled it
- Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium.Cancer discovery · 2021Trial
- A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†.Annals of oncology : official journal of the European Society for Medical Oncology · 2015Trial
- Review
- Resistance to the KRASG12D Inhibitor MRTX1133 Is Associated with Increased Sensitivity to BET Inhibition.Molecular cancer therapeutics · 2026Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Efficacy of dual KRASCell death & disease · 2026Article
- Immunogenic cell death and tertiary lymphoid structures jointly define dysregulated antitumor immune states and therapeutic vulnerability in lung adenocarcinoma.Frontiers in immunology · 2026Article
- BCL-2 Family Inhibition Enhances mTORC1/2 Inhibition in PIK3CA-Mutant Colorectal Cancer.Molecular cancer therapeutics · 2025Article
- BOGO: A Proteome-Wide Gene Overexpression Platform for Discovering Rational Cancer Combination Therapies.bioRxiv : the preprint server for biology · 2025Article
- Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.Health science reports · 2025Article
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress.Nature communications · 2025Article
- LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers.Nature communications · 2025Article
- Tracing specificity of immune landscape remodeling associated with distinct anticancer treatments.iScience · 2025Article
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer.Cancer research · 2024Article
- BCL-XScience advances · 2024Article
179 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
KRAS is the most commonly mutated oncogene, yet no effective targeted therapies exist for KRAS mutant cancers. We developed a pooled shRNA-drug screen strategy to identify genes that, when inhibited, cooperate with MEK inhibitors to effectively treat KRAS mutant cancer cells. The anti-apoptotic BH3 family gene BCL-XL emerged as a top hit through this approach. ABT-263 (navitoclax), a chemical inhibitor that blocks the ability of BCL-XL to bind and inhibit pro-apoptotic proteins, in combination with a MEK inhibitor led to dramatic apoptosis in many KRAS mutant cell lines from different tissue types. This combination caused marked in vivo tumor regressions in KRAS mutant xenografts and in a genetically engineered KRAS-driven lung cancer mouse model, supporting combined BCL-XL/MEK inhibition as a potential therapeutic approach for KRAS mutant cancers.
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What OpenQuestion holds
Registered trials
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.