ArticleEMBO molecular medicine2020
Combined targeting of G protein-coupled receptor and EGF receptor signaling overcomes resistance to PI3K pathway inhibitors in PTEN-null triple negative breast cancer.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination therapies.Clinical and experimental medicine · 2026Review
- PIK3CA mutations and PI3K isoform expression define prognostic signatures in ovarian clear cell carcinoma.Archives of gynecology and obstetrics · 2026Article
- Cancer signaling networks in tumor progression and drug resistance: Crosstalk, adaptive reprogramming and therapeutic targeting (Review).Oncology reports · 2026Review
- The mechanistic role of the thromboxane A2 receptor (TBXA2R) in non-small cell lung cancer (NSCLC).Cancer cell international · 2026Article
- FNDC1 Competitively Binds Gβ2 to Suppress the β-Catenin-Destruction Complex and Promote Gastric Cancer Malignancy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer.Scientific reports · 2025Article
- An immune-related seven-gene signature for predicting lymph node metastasis in breast cancer.Frontiers in molecular biosciences · 2025Article
- Cancer Cell's Achilles Heels: Considerations for Design of Anti-Cancer Drug Combinations.International journal of molecular sciences · 2024Article
- RSPO3 induced by Helicobacter pylori extracts promotes gastric cancer stem cell properties through the GNG7/β-catenin signaling pathway.Cancer medicine · 2024Article
- Synthetic lethal approaches to target cancers with loss of PTEN function.Genes & diseases · 2023Article
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Survival is associated with repressive histone trimethylation markers in both HR-positive HER2-negative and triple-negative breast cancer patients.Virchows Archiv : an international journal of pathology · 2023Article
- Targeting Class I-II-III PI3Ks in Cancer Therapy: Recent Advances in Tumor Biology and Preclinical Research.Cancers · 2023Review
- Article
- Review
- Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling.International journal of medical sciences · 2022Article
- Synthesis and Biological Evaluation of (Pharmaceuticals (Basel, Switzerland) · 2021Article
- Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- SOX4 and SMARCA4 cooperatively regulate PI3k signaling through transcriptional activation of TGFBR2.NPJ breast cancer · 2021Article
- Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) has poorer prognosis compared to other types of breast cancers due to the lack of effective therapies and markers for patient stratification. Loss of PTEN tumor suppressor gene expression is a frequent event in TNBC, resulting in over-activation of the PI 3-kinase (PI3K) pathway and sensitivity to its inhibition. However, PI3K pathway inhibitors show limited efficacy as monotherapies on these tumors. We report a whole-genome screen to identify targets whose inhibition enhanced the effects of different PI3K pathway inhibitors on PTEN-null TNBC. This identified a signaling network that relies on both the G protein-coupled receptor for thrombin (PAR1/F2R) and downstream G protein βγ subunits and also epidermal growth factor receptor (EGFR) for the activation of the PI3K isoform p110β and AKT. Compensation mechanisms involving these two branches of the pathway could bypass PI3K blockade, but combination targeting of both EGFR and PI3Kβ suppressed ribosomal protein S6 phosphorylation and exerted anti-tumor activity both in vitro and in vivo, suggesting a new potential therapeutic strategy for PTEN-null TNBC.
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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.