The DOI matches its Crossref record; 129 of the 131 references it cites were found in a registry or an index.
Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway
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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“AKT/mTOR/HIF1α signaling has been suggested to play critical roles in promoting glycolysis and lactate production and thus in the “metabolic reprogramming” of cancer cells24–28.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [24]
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Cites
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Research works printed but not linked: 1
- Janku, 2011, Loss of PTEN expression in patients treated with PI3K/AKT/mTOR signaling pathway inhibitors, Cancer Res, 71
Cited by
Sorted by citations
Targeting the PI3K pathway in cancer: are we making headway?
Janku, F., Yap, T. A., & Meric-Bernstam, F. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.28 · Cited by 1,033
A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer
Braicu, C., Buse, M., Busuioc, C. I., Drulă, R., Gulei, D., Ráduly, L., Alexandru Vasile, R. U. S. U., Irimie, A., Atanasov, A. G., Slaby, O., et al. (2019) · Cancers · doi:10.3390/cancers11101618 · Cited by 940
Zhang, X., Wang, S., Wang, H., Cao, J., Huang, X., Chen, Z., Xu, P., Sun, G., Xu, J., Lv, J., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-018-0935-5 · Cited by 832
RetractedAttacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer
Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 818
Health benefits of polyphenols: A concise review
Rana, A., Samtiya, M., Dhewa, T., Mishra, V., & Aluko, R. E. (2022) · Journal of Food Biochemistry · doi:10.1111/jfbc.14264 · Cited by 840
Metadata
- 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)
- 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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