Evidence map›Paper›PMID 40117718›Full record

ArticleNeoplasia (New York, N.Y.)2025

Anti-PD1 prolongs the response of PI3K and farnesyl transferase inhibition in HRAS- and PIK3CA-mutant head and neck cancers.

Dinesh Babu Manikandan, Sankar Jagadeeshan, Sooraj Mathukkada, Raghda Abu Shareb, Manu Prasad, Liju Vijaya Steltar Belsamma, Divyasree Marripati, Noga Erez, Monica Wainer, Amit Geva and 9 more

Abstract read
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In one paragraph

Article in Neoplasia (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

19 authors.

Dinesh Babu ManikandanThe 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.
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.
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.
Raghda Abu SharebThe 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.
Manu PrasadThe 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; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
Liju Vijaya Steltar BelsammaThe 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.
Divyasree MarripatiThe 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.
Noga ErezThe 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.
Monica WainerThe 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.
Amit GevaThe 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.
Danielle RavivThe 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.
Irit AllonFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Institute of Pathology, Barzilai University Medical Center, Ashqelon, Israel.
Luc Gt MorrisDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
Gloria H SuHerbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA; Department of Pathology, Columbia University Medical Center, New York, NY, USA; Department of Otolaryngology/Head and Neck Surgery, Columbia University Medical Center, New York, NY, USA.
Hai WangCAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, and University of Chinese Academy of Sciences, Beijing, China.
Ari J RosenbergDepartment of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Linda KesslerKura Oncology, Inc., San Diego, CA, USA.
Francis BurrowsKura Oncology, Inc., San Diego, CA, 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.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundTipifarnib, a farnesyl transferase inhibitor, has shown promising response in the treatment of HRAS-mutant HNSCC in the clinic, and in combination with a PI3K inhibitor in PIK3CA-mutant mouse models; however, the involvement of antitumor immunity in the efficacy of tipifarnib has not yet been investigated. This study aimed to evaluate the involvement of antitumor immunity in the efficacy of tipifarnib in HRAS- or PIK3CA-mutant HPV-positive and HPV-negative head and neck cancer murine models.

methodsTo investigate the role of antitumor immunity, we compared the efficacy of tipifarnib in immune-intact C57BL/6 mice and immunodeficient NSG mice. Histopathological analyses were conducted to evaluate PD-L1 expression and the activation of key signaling pathways. Additionally, the synergistic potential of tipifarnib with the PI3Kα inhibitor alpelisib (BYL719) was assessed in vitro and in vivo. Immunohistochemical analysis was performed to examine the infiltration of CD8

resultsIn the HPV-positive HRAS-mutant HNSCC model, the antitumor efficacy of tipifarnib was primarily dependent on CD8

conclusionThese findings underscore the critical role of antitumor immunity, particularly CD8

Indexed as

Class I Phosphatidylinositol 3-KinasesFarnesyltranstransferaseHead and Neck NeoplasmsImmune Checkpoint InhibitorsMutationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins p21(ras)AnimalsCD8-Positive T-LymphocytesCell Line, TumorDisease Models, AnimalFemaleHumansMicePhosphoinositide-3 Kinase InhibitorsQuinolonesAlpelisibClass I Phosphatidylinositol 3-KinasesFarnesyltranstransferaseImmune Checkpoint InhibitorsPhosphoinositide-3 Kinase InhibitorsPIK3CA protein, humanPik3ca protein, mouseProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins p21(ras)QuinolonesThiazolestipifarnibAlpelisibAnti-PD1Head and neck cancerHRASPI3KTipifarnib

Identifiers

PMID40117718
PMCPMC11978339

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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.