Cited by 773PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerAdvanced Breast Cancer Therapies

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Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway

Polivka, Jiri, Janku, Filip·2014·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2013.12.004

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Abstract

Aberrations in various cellular signaling pathways are instrumental in regulating cellular metabolism, tumor development, growth, proliferation, metastasis and cytoskeletal reorganization. The fundamental cellular signaling cascade involved in these processes, the phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR), closely related to the mitogen-activated protein kinase (MAPK) pathway, is a crucial and intensively explored intracellular signaling pathway in tumorigenesis. Various activating mutations in oncogenes together with the inactivation of tumor suppressor genes are found in diverse malignancies across almost all members of the pathway. Substantial progress in uncovering PI3K/AKT/mTOR alterations and their roles in tumorigenesis has enabled the development of novel targeted molecules with potential for developing efficacious anticancer treatment. Two approved anticancer drugs, everolimus and temsirolimus, exemplify targeted inhibition of PI3K/AKT/mTOR in the clinic and many others are in preclinical development as well as being tested in early clinical trials for many different types of cancer. This review focuses on targeted PI3K/AKT/mTOR signaling from the perspective of novel molecular targets for cancer therapy found in key pathway members and their corresponding experimental therapeutic agents. Various aberrant prognostic and predictive biomarkers are also discussed and examples are given. Novel approaches to PI3K/AKT/mTOR pathway inhibition together with a better understanding of prognostic and predictive markers have the potential to significantly improve the future care of cancer patients in the current era of personalized cancer medicine.

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Authors: Polivka, J., & Janku, F.
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2014-05
Volume: 142
Issue: 2
Pages: 164-175
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2013.12.004
OpenAlex: W2132052921
Cited by: 765
References: 131
Citations by year: 2026: 20 · 2025: 31 · 2024: 41 · 2023: 71 · 2022: 56 · 2021: 90 · 2020: 80 · 2019: 103 · 2018: 63 · 2017: 71 · 2016: 51 · 2015: 59 · 2014: 28
FWCI: 4.39
Type: journal article
Language: en
Open access: closed
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
Keywords: PI3K/AKT/mTOR pathway, targeted cancer therapy, molecular targets, PI3K inhibitors, mTOR inhibitors, everolimus, temsirolimus, MAPK signaling, oncogenic mutations, tumor suppressor, prognostic factors, predictive biomarkers, precision oncology, carcinogenesis
MeSH terms: Phosphoinositide-3 Kinase Inhibitors, Animals, Antineoplastic Agents, Humans, Neoplasms, Drug Design, Signal Transduction, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-Kinase, TOR Serine-Threonine Kinases, Molecular Targeted Therapy

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Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway

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