ArticleBreast cancer research and treatment2023
Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer.
Article in Breast cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03767335 (Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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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.
Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable (Advanced) or Metastatic (a/m) Breast Cancer Progressed to Anti-HER2 Based Therapy
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Efficacy and Safety of Phosphatidylinositol 3-kinase Inhibitors for Patients with Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.Current cancer drug targets · 2024Pooled it
- Targeting PI3Kδ for lymphoma and immune diseases treatment: a review.Molecular diversity · 2026Review
- A Perspective of PI3K/AKT/mTOR Pathway Inhibitors to Overcome Drug-resistance in Breast Cancer Therapy.Current medicinal chemistry · 2025Review
- Clinicopathological and prognostic analysis of PIK3CA mutated invasive breast cancer in Chinese women.Clinics (Sao Paulo, Brazil) · 2025Article
- PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.Breast cancer (Tokyo, Japan) · 2024Review
- The activity of a PI3K δ-sparing inhibitor, MEN1611, in non-small cell lung cancer cells with constitutive activation of the PI3K/AKT/mTOR pathway.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeDysregulation of the PI3K pathway is one of the most common events in breast cancer. Here we investigate the activity of the PI3K inhibitor MEN1611 at both molecular and phenotypic levels by dissecting and comparing its profile and efficacy in HER2 + breast cancer models with other PI3K inhibitors.
methodsModels with different genetic backgrounds were used to investigate the pharmacological profile of MEN1611 against other PI3K inhibitors. In vitro studies evaluated cell viability, PI3K signaling, and cell death upon treatment with MEN1611. In vivo efficacy of the compound was investigated in cell line- and patient-derived xenografts models.
resultsConsistent with its biochemical selectivity, MEN1611 demonstrated lower cytotoxic activity in a p110δ-driven cellular model when compared to taselisib, and higher cytotoxic activity in the p110β-driven cellular model when compared to alpelisib. Moreover, MEN1611 selectively decreased the p110α protein levels in PIK3CA mutated breast cancer cells in a concentration- and proteasome-dependent manner. In vivo, MEN1611 monotherapy showed significant and durable antitumor activity in several trastuzumab-resistant PIK3CA-mutant HER2 + PDX models. The combination of trastuzumab and MEN1611 significantly improved the efficacy compared to single agent treatment.
conclusionsThe profile of MEN1611 and its antitumoral activity suggest an improved profile as compared to pan-inhibitors, which are limited by a less than ideal safety profile, and isoform selective molecules, which may potentially promote development of resistance mechanisms. The compelling antitumor activity in combination with trastuzumab in HER2 + trastuzumab-resistant, PIK3CA mutated breast cancer models is at the basis of the ongoing B-Precise clinical trial (NCT03767335).
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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.