Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Everolimus is a mTOR inhibitor which demonstrates clinical activity in several solid tumors, especially in kidney cancer after first line TKI anti VEGF treatment and in breast cancer in association with exemesthane after failure of aroamatase inhibitors. The purpose of this study was to analyze in clinical practice the tolerance of everolimus in patients with breast cancer and kidney cancer. We conducted a retrospective study on patients followed up for breast cancer and kidney cancer over the period January 2008 - January 2015. All patients received everolimus at a dosage of 10 mg/day alone or in association with exemesthane for breast cancer. Adverse reactions were classified according to the National Cancer Institute Common Terminology Criteria for Adverses version 4.0 (NCI-CTCAE). A total of 100 patients were enrolled in the study: 76 patients with breast cancer and 24 patients with kidney cancer. The median follow-up period was 5.7 months. Treatment was stopped in more than 70% of the cases because of intolerance. The main adverse events, with a prevalence of more than 30% for all grades were mucositis, rash, fatigue, anemia, lymphopenia, hyperglycaemia, hyperlipidemia and infections. Mucositis, noninfectious pneumopathies and infections had high incidence of toxicity grade 3-4. Treatment discontinuation rate due to intolerance is high compared to literature data. At the beginning of treatment, particular attention should be given to mucositis, the immunosuppressive effect of treatment and non-infectious pneumopathies.
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PMID:[Tolerablity of everolimus in clinical practice: a retrospective study]. 3277 3

Recently many therapeutic classes have emerged in advanced hormone receptor-positive breast cancer, which is the leading cause of cancer death in women. In absence of visceral crisis, treatment relies on endocrine therapy combined with cyclin dependent kinase 4 and 6 inhibitor. Many mechanisms lead to resistance to endocrine therapy, including the activation of intracellular signaling pathways critical for cell survival. Approximately 70% of breast tumors harbor an alteration in the phosphoinositide 3 kinase (PI3K)/Akt pathway, leading to its hyper activation. This pathway is involved in the regulation of growth, proliferation and cell survival as well as in angiogenesis and is consequently a major target in the oncogenesis. An aberrant PIK3CA mutation is a common phenomenon in breast cancer and found in approximately 40% of patients with advanced hormone receptor-positive breast cancer. For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes).
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PMID:Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer. 3278 89


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