ReviewCancer discovery2019
Challenges for the Clinical Development of PI3K Inhibitors: Strategies to Improve Their Impact in Solid Tumors.
Review in Cancer discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 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
147 citing papers in PubMed, 256 citations in OpenAlex.
- Add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: a randomized phase 3 study.The oncologist · 2026Trial
- Phase II Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H.JCO precision oncology · 2025Trial
- Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Trial
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- Targeting the PI3K/AKT/mTOR pathway in gastrointestinal cancers: a comprehensive review of mechanisms, preclinical evidence, and clinical challenges.Medical oncology (Northwood, London, England) · 2026Review
- Evidence That the Protein Phosphatase Activity of PTEN Contributes to Embryonic Development and Tumor Suppression.Cancer science · 2026Article
- Pictilisib and nutrient stress synergize to induce methuosis via PI(4,5)PCell death & disease · 2026Article
- Age distinguishes selection from causation in cancer genomes.Nature genetics · 2026Article
- Synergistic Inhibition of Colorectal Cancer Growth by Combined PI3K and COX-2 Blockade in Cell Lines and Patient-Derived Organoids.Pharmaceutics · 2026Article
- DNA-PKcs promotes therapy resistance and metastatic recurrence in neuroblastoma.Cancer letters · 2026Article
- Review
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- Macrophages: Targets for next-generation cancer immunotherapy.Cancer cell · 2026Review
- SR-B1 knockdown suppresses breast cancer cell proliferation, migration, and invasion via the PI3K/AKT pathway.Einstein (Sao Paulo, Brazil) · 2026Article
- KRAS Codon-Specific Mutations Differentially Toggle PI3K Pathway Signaling and Alter Sensitivity to Inavolisib (GDC-0077).Molecular cancer therapeutics · 2025Article
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Beyond base camp: PI3K/mTOR inhibition for the treatment of pediatric high-grade gliomas.Neuro-oncology · 2025Review
- MYB/AKT3 axis is a key driver of ovarian cancer growth, aggressiveness, and chemoresistance.Journal of ovarian research · 2025Article
- Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The PI3K pathway is mutated and aberrantly activated in many cancers and plays a central role in tumor cell proliferation and survival, making it a rational therapeutic target. Until recently, however, results from clinical trials with PI3K inhibitors in solid tumors have been largely disappointing. Here, we describe several factors that have limited the success of these agents, including the weak driver oncogenic activity of mutant PI3K, suboptimal patient selection in trials, drug-related toxicities, feedback upregulation of compensatory mechanisms when PI3K is blocked, increased insulin production upon PI3Kα inhibition, lack of mutant-specific inhibitors, and a relative scarcity of studies using combinations with PI3K antagonists. We also suggest strategies to improve the impact of these agents in solid tumors. Despite these challenges, we are optimistic that isoform-specific PI3K inhibitors, particularly in combination with other agents, may be valuable in treating appropriately selected patients with PI3K-dependent tumors. SIGNIFICANCE: Despite the modest clinical activity of PI3K inhibitors in solid tumors, there is an increasing understanding of the factors that may have limited their success. Strategies to ameliorate drug-related toxicities, use of rational combinations with PI3K antagonists, development of mutant-selective PI3K inhibitors, and better patient selection should improve the success of these targeted agents against solid tumors.
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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.