Second-generation mTOR inhibitors and dual mTOR-phosphatidylinositolkinase inhibitors are currently being evaluated in clinical trials. This work is published and licensed by Dove Medical Press Limited. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
Both BEZ and XL have shown good tolerability, with adverse effects including diarrhea, anorexia, and nausea [ 49 ]. Advances in molecular research have resulted in an improved understanding of cancer biology. However, rational clinical trials design with a focus in identifying a patient population most likely to benefit from this strategy is imperative to the success of single-agent therapeutics.
The successful development of the combinations will require determining the duration, doses, and schedules of targeted therapy and how to best incorporate it into standard treatment protocols. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. We are IntechOpen, the world's leading publisher of Open Access books. Built by scientists, for scientists.
Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Table 1. The PI3K proteins family.
mTOR Inhibition for Cancer Therapy: Past, Present and Future
AKT inhibitors in cancer therapy AKT inhibitors constitute another class of drugs that has gained recent interest. Rapamycin and its derivatives As discussed previously, mTOR is involved in many cell signaling pathways, and clinical trials for cancer treatment showed that tumor cells with mutations in p53 or PTEN are susceptible to mTOR inhibitors [ ]. Table 2. More Print chapter. How to cite and reference Link to this chapter Copy to clipboard.
Cite this chapter Copy to clipboard Isabella S. Rangel October 28th Available from:. Over 21, IntechOpen readers like this topic Help us write another book on this subject and reach those readers Suggest a book topic Books open for submissions. More statistics for editors and authors Login to your personal dashboard for more detailed statistics on your publications. Access personal reporting. More About Us. Gene name human. Trade name company. Drug target. Development stage. Tumor types. Pan-PI3K inhibitor. Buparlisib Novartis. Non-small cell lung cancer, prostate, breast, GBM, colon.
Use of mTOR inhibitors in the treatment of breast cancer: an evaluatio | BCTT
Solid cancers, breast, breast, endometrial, ovarian, non-small cell lung cancer, glioblastoma, lymphoma. Pictilisib Genentech-Roche. Solid cancers, breast, non-small cell lung cancer, glioblastoma, non-Hodgkin's lymphoma. Solid cancers PTEN deficient , prostate.
Predictive factors of response to mTOR inhibitors in neuroendocrine tumours
Alpelisib Novartis. Taselisib Genentech. Solid cancers, breast, non-small cell lung cancer.
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Idelalisib Gilead Sciences. Lymphomas, multiple myelomas, chronic lymphocytic leukemia, acute myeloid leukemia.
Perifosine Pfizer. AKT inhibitors. Solid tumors, non-small cell lung cancer, colon, kidney, breast, gliomas, multiple myeloma, leukemia, lymphomas. Hematologic malignancies. Sirolimus Wyeth. Glioblastoma, non-small cell lung cancer. Everolimus Novartis. Metastatic renal cell carcinoma, breast cancer, melanoma, ovarian cancer, neuroendocrine tumors of the pancreatic origin PNET , endometrial carcinoma.
Despite the proven efficacy of endocrine treatments, intrinsic de novo and acquired endocrine resistance occurs in a significant percentage of patients. Different molecular mechanisms have been proposed as the causes of endocrine resistance, including loss of ER expression, altered activity of ER co-regulators, deregulation of apoptosis and cell cycle, ER gene mutations, and hyperactive receptor tyrosine kinase RTK downstream pathways [ 2 ]. The first is activated when estrogens bind ER protein leading to the formation of a transcription machinery that exerts the so-called ER classical genomic activity, by directly binding specific promoter regions of target genes, known as ER elements EREs [ 3 ].
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Of note, ER classical genomic activity is effectively inhibited by endocrine agents. Moreover, it can also modulate both alternative genomic and non-genomic ER activities, and ultimately sustain resistant cell growth [ 3 ]. This in turn phosphorylates several molecules, including TSC2 with consequent activation of the mTOR complex, and ER itself, leading to its activation in a ligand-independent manner [ 4 ].
The study showed a remarkable improvement in median progression-free survival PFS for the experimental arm 6. Nevertheless, no statistically significant difference in overall survival OS was found, despite a numerical advantage of the experimental arm In this study, which enrolled postmenopausal patients pre-treated with an AI in the adjuvant or metastatic disease setting, PFS was significantly improved by the combination arm compared with fulvestrant alone The everolimus-fulvestrant arm was associated with higher toxicity than the control arm, in agreement with that observed in the BOLERO2 trial [ 12 ].
In this smaller group, median PFS was 3.