Evidence map›Paper›PMID 24481312›Full record

ReviewNature reviews. Drug discovery2014

PI3K and cancer: lessons, challenges and opportunities.

David A Fruman, Christian Rommel

Registry-linked trialAbstract readReview
In one paragraph

Review in Nature reviews. Drug discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07486648 (The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer), which is not on this map. Cited by 935 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
935citing papers in PubMed, 1 pooled it
102.4field-weighted citation impact, top 1% 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.

NCT07486648 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer (NSCLC) Participants With PIK3CA/AKT1/PTEN Alterations Who Had Progressed on First-line Osimertinib Monotherapy or Plus Chemotherapy: a First-in-human, Phase Ib/Ⅱa Study (PRECISION)

TypeinterventionalSponsorShanxi Province Cancer HospitalRan2026 to 2028Enrolled53ConditionsLung Cancer (NSCLC), Lung Cancer (Non-Small Cell), Advanced Non-small-cell Lung CancerArmsCapivasertib in combination with Osimertinib
3 · Its place in the literature

Who cites it

935 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,716 citations in OpenAlex.

  1. Pooled it
  2. The novel [RSC advances · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Phase I Trial of Ipatasertib plus Atezolizumab Enhances PI3K/AKT Pathway Immune Responses in Solid Tumors and Refractory Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

875 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

David A FrumanDepartment of Molecular Biology & Biochemistry, and Institute for Immunology, University of California, Irvine, 3242 McGaugh Hall, Irvine, California 92697, USA.
Christian RommelAmgen Inc., Thousand Oaks, One Amgen Center Drive, California 91320, USA.
Amgen (United States) · USUniversity of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
TOR kinase inhibitors for leukemia therapy: mechanisms of action and resistanceR01CA158383 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI FRUMAN, DAVID ALEXANDER · 2012 to 2016
$1.5M
Solving the elusive mechanism of rapamycin action in lymphocytesR21AI099656 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI FRUMAN, DAVID ALEXANDER · 2012 to 2013
$409k
NCI NIH HHS CA158383NCI NIH HHS P30 CA062203NCI NIH HHS P30CA62203NCI NIH HHS R01 CA158383NIAID NIH HHS AI099656NIAID NIH HHS R21 AI099656
6 · The paper itself

Abstract

The central role of phosphoinositide 3-kinase (PI3K) activation in tumour cell biology has prompted a sizeable effort to target PI3K and/or downstream kinases such as AKT and mammalian target of rapamycin (mTOR) in cancer. However, emerging clinical data show limited single-agent activity of inhibitors targeting PI3K, AKT or mTOR at tolerated doses. One exception is the response to PI3Kδ inhibitors in chronic lymphocytic leukaemia, where a combination of cell-intrinsic and -extrinsic activities drive efficacy. Here, we review key challenges and opportunities for the clinical development of inhibitors targeting the PI3K-AKT-mTOR pathway. Through a greater focus on patient selection, increased understanding of immune modulation and strategic application of rational combinations, it should be possible to realize the potential of this promising class of targeted anticancer agents.

Indexed as

Drug DiscoveryPhosphoinositide-3 Kinase InhibitorsAnimalsAntineoplastic AgentsClinical Trials as TopicEnzyme InhibitorsHumansNeoplasmsProto-Oncogene Proteins c-aktReceptor Cross-TalkSignal TransductionTOR Serine-Threonine KinasesAntineoplastic AgentsEnzyme InhibitorsPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinases

Identifiers

PMID24481312
PMCPMC3994981
OpenAlexW2054917860

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.