ArticleBritish journal of cancer2024
Farnesyl-transferase inhibitors show synergistic anticancer effects in combination with novel KRAS-G12C inhibitors.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 27 citations in OpenAlex.
- M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors.Oncogene · 2026Article
- Exceptional treatment responses and molecular markers among 103 colorectal cancer cell lines.Molecular biomedicine · 2026Article
- Renaissance of farnesyltransferase inhibitors in cancer.Journal of translational medicine · 2026Review
- The Farnesyl Transferase Inhibitor Darlifarnib (KO-2806) Resensitizes Relapsing Tumors to RAS Inhibition.Cancer research · 2026Article
- Combining cutting edge computational and experimental methods for targeting KRAS mutations in non-small cell lung cancer.Expert opinion on drug discovery · 2026Review
- Nuclear Mechanotransduction Across the Metastatic Cascade: Decoding Spatiotemporal Heterogeneity in Cancer Dissemination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting the Ras-Ral Signaling Axis in Type 2 Diabetes Mellitus: A Dual-Modulation Approach to Correcting Insulin Resistance and β-Cell Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation.Cell communication and signaling : CCS · 2026Article
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- Antimetastatic effects of MRTX1133 KRAS G12D specific inhibitor in a liver metastatic model of pancreatic ductal adenocarcinoma.Scientific reports · 2026Article
- Integrative computational approach to farnesyltransferase inhibition toward anti-liver cancer drug candidate fromMolecular biology research communications · 2026Article
- Modeling response to the KRAS-G12C inhibitor AZD4625 in KRASBritish journal of cancer · 2026Article
- Unravelling Resistance: Integrating Metabolism, Epigenetics, Immunology, and Proteostasis in Strategies against Kirsten Rat Sarcoma Viral Oncogene Homolog-mutant Colorectal Cancer.International journal of biological sciences · 2026Review
- WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASCell death & disease · 2025Article
- Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment.The Journal of clinical investigation · 2025Article
- The complex journey of targeting RAS in oncology.BMC cancer · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- A novel signature predicts prognosis in pancreatic cancer based on tumor membrane-associated genes.Heliyon · 2025Article
- Impaired MC3T3-E1 osteoblast differentiation triggered by oncogenic HRAS is rescued by the farnesyltransferase inhibitor Tipifarnib.Scientific reports · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundInhibition of mutant KRAS challenged cancer research for decades. Recently, allele-specific inhibitors were approved for the treatment of KRAS-G12C mutant lung cancer. However, de novo and acquired resistance limit their efficacy and several combinations are in clinical development. Our study shows the potential of combining G12C inhibitors with farnesyl-transferase inhibitors.
methodsCombinations of clinically approved farnesyl-transferase inhibitors and KRAS G12C inhibitors are tested on human lung, colorectal and pancreatic adenocarcinoma cells in vitro in 2D, 3D and subcutaneous xenograft models of lung adenocarcinoma. Treatment effects on migration, proliferation, apoptosis, farnesylation and RAS signaling were measured by histopathological analyses, videomicroscopy, cell cycle analyses, immunoblot, immunofluorescence and RAS pulldown.
resultsCombination of tipifarnib with sotorasib shows synergistic inhibitory effects on lung adenocarcinoma cells in vitro in 2D and 3D. Mechanistically, we present antiproliferative effect of the combination and interference with compensatory HRAS activation and RHEB and lamin farnesylation. Enhanced efficacy of sotorasib in combination with tipifarnib is recapitulated in the subcutaneous xenograft model of lung adenocarcinoma. Finally, combination of additional KRAS G1C and farnesyl-transferase inhibitors also shows synergism in lung, colorectal and pancreatic adenocarcinoma cellular models. DISCUSSION: Our findings warrant the clinical exploration of KRAS-G12C inhibitors in combination with farnesyl-transferase inhibitors.
Indexed as
Identifiers
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.