ArticleCancer research2023
Tipifarnib Potentiates the Antitumor Effects of PI3Kα Inhibition in PIK3CA- and HRAS-Dysregulated HNSCC via Convergent Inhibition of mTOR Activity.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 28 citations in OpenAlex.
- Farnesyl Transferase Inhibitor KO-2806 (Darlifarnib) Enhances the Antitumor Activity of Tyrosine Kinase Inhibitors in RCC.Molecular cancer therapeutics · 2026Article
- Benefits and challenges of adding BKM120 to a BI-3406 plus trametinib combination therapy.BMC cancer · 2026Article
- Renaissance of farnesyltransferase inhibitors in cancer.Journal of translational medicine · 2026Review
- Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.Nature chemical biology · 2026Article
- The Farnesyl Transferase Inhibitor Darlifarnib (KO-2806) Resensitizes Relapsing Tumors to RAS Inhibition.Cancer research · 2026Article
- The Role of Molecular Testing in Head and Neck Squamous Cell Carcinoma of Unknown Primary.Head and neck pathology · 2026Review
- Model-Based Patient Selection and Dosing Strategies for HRAS and PIK3CA Dysregulated HNSCC: A QSP Model for Alpelisib and Tipifarnib Combination.Clinical pharmacology and therapeutics · 2026Article
- Current and Emerging Protein Biomarkers for the Diagnosis and Prognosis of Head and Neck Cancer.Genes · 2025Review
- Review
- Wild-type RAS signaling is an essential therapeutic target inScience signaling · 2025Article
- Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.BMC biology · 2025Article
- Anti-PD1 prolongs the response of PI3K and farnesyl transferase inhibition in HRAS- and PIK3CA-mutant head and neck cancers.Neoplasia (New York, N.Y.) · 2025Article
- Programmed cell death protein 1 in cancer cells.Cell communication and signaling : CCS · 2025Review
- Functional-proteomics-based investigation of the cellular response to farnesyltransferase inhibition in lung cancer.iScience · 2025Article
- Alpelisib and Immunotherapy: A Promising Combination for Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.Cancer reports (Hoboken, N.J.) · 2024Article
- Head and neck cancer: pathogenesis and targeted therapy.MedComm · 2024Review
- Tipifarnib physiologically-based pharmacokinetic modeling to assess drug-drug interaction, organ impairment, and biopharmaceutics in healthy subjects and cancer patients.CPT: pharmacometrics & systems pharmacology · 2024Article
- Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure.Circulation research · 2024Article
- "Tip" the Scale of Cardiac Repair via Reducing Pathological Extracellular Vesicles.Circulation research · 2024Article
- Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.Cells · 2024Review
Corrections and comments
- Commented on by
Authors and funding
23 authors at 8 institutions in 1 country.
Funding
Abstract
Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival (OS) ranging from 6 to 18 months. For those who progress on standard-of-care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase (FTase) inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. Tipifarnib synergized with alpelisib at the level of mTOR in PI3Kα- or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor regression in vivo. On the basis of these findings, the KURRENT-HN trial was launched to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC. Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy. Combined alpelisib and tipifarnib has potential to benefit >45% of patients with R/M HNSCC. By blocking feedback reactivation of mTORC1, tipifarnib may prevent adaptive resistance to additional targeted therapies, enhancing their clinical utility. SIGNIFICANCE: The mechanistically designed, biomarker-matched strategy of combining alpelisib and tipifarnib is efficacious in PIK3CA- and HRAS-dysregulated head and neck squamous carcinoma and could improve outcomes for many patients with recurrent, metastatic disease. See related commentary by Lee et al., p. 3162.
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.