Evidence map›Paper›PMID 38219706›Full record

ArticleOral oncology2024

Evolutionary dynamics of tipifarnib in HRAS mutated head and neck squamous cell carcinoma.

Sankar Jagadeeshan, Kushal Suryamohan, Nara Shin, Sooraj Mathukkada, Alexandra Boyko, Daria Melikhova, Anastasia Tsareva, Leysan Yunusova, Ekaterina Pravdivtseva, Danil Stupichev and 13 more

Open access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Oral oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Dual inhibition of HERs and PD-1 counteract resistance in KRASJournal of experimental & clinical cancer research : CR · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 4 institutions in 2 countries.

Sankar JagadeeshanThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Kushal SuryamohanBostonGene Corporation, Waltham, MA, USA.
Nara ShinBostonGene Corporation, Waltham, MA, USA.
Sooraj MathukkadaThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Alexandra BoykoBostonGene Corporation, Waltham, MA, USA.
Daria MelikhovaBostonGene Corporation, Waltham, MA, USA.
Anastasia TsarevaBostonGene Corporation, Waltham, MA, USA.
Leysan YunusovaBostonGene Corporation, Waltham, MA, USA.
Ekaterina PravdivtsevaBostonGene Corporation, Waltham, MA, USA.
Danil StupichevBostonGene Corporation, Waltham, MA, USA.
Kirill ShaposhnikovBostonGene Corporation, Waltham, MA, USA.
Angela PetersonBostonGene Corporation, Waltham, MA, USA.
Lev BednyaginBostonGene Corporation, Waltham, MA, USA.
Eduardo Shugaev-MendosaBostonGene Corporation, Waltham, MA, USA.
Linda KesslerKura Oncology, Inc., San Diego, CA, USA.
Francis BurrowsKura Oncology, Inc., San Diego, CA, USA.
Alan L HoMemorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York City, NY, USA.
Nishant AgrawalDepartment of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, IL, USA.
Alexander T PearsonDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Evgeny IzumchenkoDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Grayson ColeDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Moshe ElkabetsThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: moshee@bgu.ac.il.
Ari J RosenbergDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. Electronic address: arirosenberg@bsd.uchicago.edu.
University of Chicago · USBen-Gurion University of the Negev · ILKura Oncology (United States) · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI CHIEN-MIN KAO · 1985 to 2026
$122.1M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014599
6 · The paper itself

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent malignancy worldwide, with a significant proportion of patients developing recurrent and/or metastatic (R/M) disease. Despite recent advances in therapy, the prognosis for patients with advanced HNSCC remains poor. Here, we present the case of a patient with recurrent metastatic HNSCC harboring an HRAS G12S mutation who achieved a durable response to treatment with tipifarnib, a selective inhibitor of farnesyltransferase. The patient was a 48-year-old woman who had previously received multiple lines of therapy with no significant clinical response. However, treatment with tipifarnib resulted in a durable partial response that lasted 8 months. Serial genomic and transcriptomic analyses demonstrated upregulation of YAP1 and AXL in metastatic lesions compared with the primary tumor, the evolution of the tumor microenvironment from an immune-enriched to a fibrotic subtype with increased angiogenesis, and activation of the PI3K/AKT/mTOR pathway in tipifarnib treatment. Lastly, in HRAS-mutated PDXs and in the syngeneic HRAS model, we demonstrated that tipifarnib efficacy is limited by activation of the AKT pathway, and dual treatment with tipifarnib and the PI3K inhibitor, BYL719, resulted in enhanced anti-tumor efficacy. Our case study highlights the potential of targeting HRAS mutations with tipifarnib in R/M HNSCC and identifies potential mechanisms of acquired resistance to tipifarnib, along with immuno-, chemo-, and radiation therapy. Preclinical results provide a firm foundation for further investigation of drug combinations of HRAS-and PI3K -targeting therapeutics in R/M HRAS-driven HNSCC.

Indexed as

Head and Neck NeoplasmsProto-Oncogene Proteins c-aktQuinolonesCell Line, TumorFemaleHumansMiddle AgedNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasesProto-Oncogene Proteins p21(ras)Squamous Cell Carcinoma of Head and NeckTumor MicroenvironmentHRAS protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)QuinolonestipifarnibDurable responseFarnesyltransferase inhibitorHead and neck squamous cell carcinomaHRAS mutationTargeted therapyTipifarnib

Identifiers

PMID38219706
PMCPMC11309563
OpenAlexW4390850000

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.