ArticleGenes & cancer2014
Amphiregulin and PTEN evoke a multimodal mechanism of acquired resistance to PI3K inhibition.
Article in Genes & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Systematic profiling of cancer-fibroblast interactions reveals drug combinations in ovarian cancer.Molecular oncology · 2025Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Targeting the PI3K Pathway: Advancements and Achievements in Breast Cancer Therapy.Current pharmaceutical design · 2025Review
- Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.Cells · 2024Review
- Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing.Disease models & mechanisms · 2018Article
- Correlation between Trop2 and amphiregulin coexpression and overall survival in gastric cancer.Cancer medicine · 2017Article
- Article
- Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Review
- Drugging PI3K in cancer: refining targets and therapeutic strategies.Current opinion in pharmacology · 2015Review
- MiR-34a suppresses amphiregulin and tumor metastatic potential of head and neck squamous cell carcinoma (HNSCC).Oncotarget · 2015Article
- A novel PI3K inhibitor PIK-C98 displays potent preclinical activity against multiple myeloma.Oncotarget · 2015Article
- Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: A phase I clinical experience.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoinositide-3 kinase (PI3K) signaling pathway alterations occur broadly in cancer and PI3K is a promising therapeutic target. Here, we investigated acquired resistance to GDC-0941, a PI3K inhibitor in clinical trials. Colorectal cancer (CRC) cells made to be resistant to GDC-0941 were discovered to secrete amphiregulin, which resulted in increased EGFR/MAPK signaling. Moreover, prolonged PI3K pathway inhibition in cultured cells over a period of months led to a secondary loss of PTEN in 40% of the CRC lines with acquired resistance to PI3K inhibition. In the absence of PI3K inhibitor, these PTEN-null PI3K inhibitor-resistant clones had elevated PI3K pathway signaling and decreased sensitivity to MAPK pathway inhibitors. Importantly, PTEN loss was not able to induce resistance to PI3K inhibitors in the absence of amphiregulin, indicating a multimodal mechanism of acquired resistance. The combination of PI3K and MAPK pathway inhibitors overcame acquired resistance in vitro and in vivo.
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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.