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Everolimus
1Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106, Freiburg, Germany. Jens.hasskarl@uniklinik-freiburg.de.
Abstract:
Everolimus (RAD001) is an oral protein kinase inhibitor of the mTOR (mammalian target of rapamycin) serine/threonine kinase signal transduction pathway. The mTOR pathway regulates cell growth, proliferation and survival, and is frequently deregulated in cancer.The EMA has approved Everolimus as Afinitor® for the treatment of hormone receptor-positive, HER2/neu-negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a nonsteroidal aromatase inhibitor, for the treatment of unresectable or metastatic, well- or moderately differentiated neuroendocrine tumors of pancreatic origin in adults with progressive disease, and for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) nonfunctional neuroendocrine tumors of gastrointestinal or lung origin in adults with progressive disease, and for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy And as Votubia® for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC), who are at risk of complications (based on factors such as tumor size or presence of aneurysm, or presence of multiple or bilateral tumors) but who do not require immediate surgery, and for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with TSC who require therapeutic intervention but are not amenable to surgery, and as an add-on treatment in patients from 2 years of age with seizures related to TSC that have not responded to other treatments ( https://www.novartis.com/news/media-releases/novartis-drug-votubiar-receives-eu-approval-treat-refractory-partial-onset ). The FDA has approved Everolimus as Afinitor® for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, after the failure of treatment with letrozole or anastrozole, for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease, for the treatment of adult patients with advanced RCC after failure of treatment with sunitinib or sorafenib, for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. for the treatment of adult and pediatric patients, 3 years of age or older, with SEGA associated with TSC who require therapeutic intervention but are not candidates for curative surgical resection. Everolimus shows promising clinical activity in additional indications. Multiple Phase II and Phase III trials of everolimus alone or in combination and will help to further elucidate the role of mTOR in oncology. For a review on everolimus as immunosuppressant, please consult other sources.
Insights
Everolimus is an oral mTOR inhibitor approved for advanced breast cancer, neuroendocrine tumors, and renal cell carcinoma. It also treats tuberous sclerosis complex-associated conditions like angiomyolipoma, SEGA, and seizures.
Area of Science:
- Oncology
- Pharmacology
Background:
- The mammalian target of rapamycin (mTOR) pathway is crucial for cell growth and survival, and its dysregulation is common in various cancers.
- Everolimus targets this pathway, offering a therapeutic strategy for cancer treatment.
Purpose of the Study:
- To summarize the approved indications and clinical activity of everolimus (RAD001) in oncology.
- To highlight its role as an oral protein kinase inhibitor targeting the mTOR pathway.
Main Methods:
- Review of European Medicines Agency (EMA) and Food and Drug Administration (FDA) approvals for Everolimus (Afinitor®, Votubia®).
- Summary of clinical trial data supporting its efficacy in various cancer types and TSC-related conditions.
Main Results:
- EMA approval for hormone receptor-positive, HER2/neu-negative advanced breast cancer, pancreatic and GI/lung neuroendocrine tumors, and advanced renal cell carcinoma.
- FDA approval for similar oncologic indications, plus renal angiomyolipoma and subependymal giant cell astrocytoma (SEGA) associated with Tuberous Sclerosis Complex (TSC), and TSC-related seizures.
Conclusions:
- Everolimus is an established therapy for multiple advanced cancers and TSC-related conditions.
- Ongoing trials continue to explore the role of mTOR inhibition in oncology.