Trial reportClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2018
Pre-surgical trial of the AKT inhibitor MK-2206 in patients with operable invasive breast cancer: a New York Cancer Consortium trial.
Trial report in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation.Breast cancer research : BCR · 2019Trial
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Balancing Risk and Efficiency in Drug Development for Rare and Challenging Tumors: A New Paradigm for Glioma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Review
- Central and peripheral emetic loci contribute to vomiting evoked by the Akt inhibitor MK-2206 in the least shrew model of emesis.European journal of pharmacology · 2021Article
- Hyperglycemia and Chemoresistance in Breast Cancer: From Cellular Mechanisms to Treatment Response.Frontiers in oncology · 2021Review
- AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?Frontiers in pharmacology · 2021Review
- Th1 cytokines in conjunction with pharmacological Akt inhibition potentiate apoptosis of breast cancer cellsOncotarget · 2020Article
- Precision Targeting ofACS central science · 2020Article
- Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035).Gynecologic oncology reports · 2020Article
- Akt Inhibition Is Associated With Favorable Immune Profile Changes Within the Tumor Microenvironment of Hormone Receptor Positive, HER2 Negative Breast Cancer.Frontiers in oncology · 2020Article
- Cellular Plasticity in Breast Cancer Progression and Therapy.Frontiers in molecular biosciences · 2020Review
- Targeting AKT for cancer therapy.Expert opinion on investigational drugs · 2019Review
- Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer.Journal of breast cancer · 2019Review
- Quantitative Imaging of Morphometric and Metabolic Signatures Reveals Heterogeneity in Drug Response of Three-Dimensional Mammary Tumor Spheroids.Molecular imaging and biology · 2019Article
- MK-2206 window of opportunity study in breast cancer.Annals of translational medicine · 2018Article
- Loss of PTEN in high grade advanced stage triple negative breast ductal cancers in African American women.Pathology, research and practice · 2018Article
- YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways.Oncotarget · 2017Article
- Unveiling changes in the landscape of patient populations in cancer early drug development.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
introductionThe PI3K/AKT/mTOR pathway is an oncogenic driver in breast cancer (BC). In this multi-center, pre-surgical study, we evaluated the tissue effects of the AKT inhibitor MK-2206 in women with stage I-III BC. MATERIALS AND
methodsTwo doses of weekly oral MK2206 were administered at days - 9 and - 2 before surgery. The primary endpoint was reduction of pAkt
resultsDespite dose reductions, the trial was discontinued after 12 patients due to grade III rash, mucositis, and pruritus. While there was a trend to reduction in pAKT after MK-2206 (p = 0.06), there was no significant change compared to controls (n = 5, p = 0.65). After MK-2206, no significant changes in ki-67, pS6, PTEN, or stathmin were observed. There was no significant association between dose level and PK (p = 0.11). Compared to controls, MK-2206 significantly increased serum glucose (p = 0.02), insulin (p < 0.01), C-peptide (p < 0.01), and a trend in IGFBP-3 (p = 0.06).
conclusionWhile a trend to pAKT reduction after MK-2206 was observed, there was no significant change compared to controls. However, the accrued population was limited, due to toxicity being greater than expected. Pre-surgical trials can identify in vivo activity in the early drug development, but side effects must be considered in this healthy population.
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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.