The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From laboratory to patients
Open accessAbstract
The phosphoinositide 3-kinase (PI3K) pathway is an intracellular signaling pathway that has regulatory roles in cell survival, proliferation, and differentiation, and a critical role in tumorigenesis. In cancer, multiple studies have investigated the therapeutic targeting of the PI3K pathway, and multiple inhibitors targeting PI3K and its isoforms, protein kinase B/AKT, mammalian target of rapamycin (mTOR), and other pathway proteins have been developed. For the treatment of solid tumors, only allosteric mTOR inhibitors, such as everolimus and temsirolimus, are currently approved for clinical use. This review describes the PI3K inhibitors that have progressed from the laboratory to late-stage clinical trials, and discusses the challenges that have prevented other compounds from doing the same. Challenges to the therapeutic effectiveness of some PI3K inhibitors include the absence of reliable and effective biomarkers, their limited efficacy as single agents, insufficient development of rational therapeutic combinations, the use of schedules with a variety of off-target effects, and suboptimal therapeutic exposures. Therefore, with regard to PI3K inhibitors currently in late-stage clinical trials, the identification of appropriate biomarkers of efficacy and the development of optimal combination regimens and dosing schedules are likely to be important for graduation into clinical practice.
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Cites
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
Baselga, J., Campone, M., Piccart, M., Burris, H. A., Rugo, H. S., Sahmoud, T., Noguchi, S., Gnant, M., Pritchard, K. I., Lebrun, F., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1109653 · Cited by 2,863
Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway
Polivka, J., & Janku, F. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.12.004 · Cited by 765
Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor
Juric, D., Castel, P., Griffith, M., Griffith, O. L., Won, H. H., Ellis, H., Ebbesen, S. H., Ainscough, B. J., Ramu, A., Iyer, G., et al. (2015) · Nature · doi:10.1038/nature13948 · Cited by 588
Bedard, P. L., Tabernero, J., Janku, F., Wainberg, Z. A., Paz-Ares, L., Vansteenkiste, J., Van Cutsem, E., Pérez-García, J., Stathis, A., Britten, C. D., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1814 · Cited by 324
van Geel, R. M. J. M., Tabernero, J., Elez, E., Bendell, J. C., Spreafico, A., Schuler, M., Yoshino, T., Delord, J.-P., Yamada, Y., Lolkema, M. P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0795 · Cited by 232
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Grilley-Olson, J. E., Bedard, P. L., Fasolo, A., Cornfeld, M., Cartee, L., Razak, A. R. A., Stayner, L.-A., Wu, Y., Greenwood, R., Singh, R., et al. (2016) · Investigational New Drugs · doi:10.1007/s10637-016-0377-0 · Cited by 81
Cited by
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
Self-citationHou, Y., Wang, K., Wan, W., Cheng, Y., Pu, X., & Ye, X. (2018) · Genes & Diseases · doi:10.1016/j.gendis.2018.06.001 · Cited by 308
Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis
Linton, M. F., Moslehi, J. J., & Babaev, V. R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112703 · Cited by 285
The Role of mTOR Signaling as a Therapeutic Target in Cancer
Popova, N. V., & Jücker, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041743 · Cited by 267
Targeted therapy in advanced non-small cell lung cancer: current advances and future trends
Majeed, U., Manochakian, R., Zhao, Y., & Lou, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01121-2 · Cited by 266
Tumor-intrinsic PIK3CA represses tumor immunogenicity in a model of pancreatic cancer
Sivaram, N., McLaughlin, P. A., Han, H. V., Petrenko, O., Jiang, Y.-P., Ballou, L. M., Pham, K., Liu, C., van der Velden, A. W. M., & Lin, R. Z. (2019) · Journal of Clinical Investigation · doi:10.1172/jci123540 · Cited by 78
Management of phosphatidylinositol-3-kinase inhibitor-associated hyperglycemia
Goncalves, M. D., & Farooki, A. (2022) · Integrative Cancer Therapies · doi:10.1177/15347354211073163 · Cited by 37
Metadata
- Authors
- Janku, F.
- Venue
- Cancer Treatment Reviews
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 59
- Pages
- 93-101
- ISSN
- 0305-7372 (ISSN-L)
- OpenAlex
- W2739301023
- Cited by
- 243
- References
- 9
- FWCI
- 10.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
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