Research and innovation in the development of everolimus for oncology Journal Article
| Authors: | Lebwohl, D.; Thomas, G.; Lane, H. A.; O'Reilly, T.; Escudier, B.; Yao, J. C.; Pavel, M.; Franz, D.; Berg, W.; Baladi, J. F.; Stewart, J.; Motzer, R. J. |
| Article Title: | Research and innovation in the development of everolimus for oncology |
| Abstract: | Introduction: The critical role of increased activity of mammalian target of rapamycin (mTOR) in the pathophysiology of multiple diseases is well established. Inhibition of the mTOR pathway may block disease progression and improve patient outcomes. Everolimus, an mTOR inhibitor, began in clinical development as part of a regimen (Certican, Zortress) for prevention of organ transplant rejection and is now an approved oncology agent. Areas covered: The objective of this review is to discuss the history of key findings and innovative cancer research undertaken to successfully develop everolimus as an oncology therapy (Afinitor) now approved for patients with advanced renal cell carcinoma (RCC) and for subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis. In addition, data for the use of everolimus in the treatment of other cancers and rare diseases are also discussed. A PubMed search of English articles without time restrictions was conducted using the search terms 'everolimus or rapamycin' and 'cancer'. Bibliographies of retrieved articles were manually searched for additional relevant articles. Major cancer congresses were also searched. Expert opinion: The clinical efficacy of everolimus alone and in combination with other agents has been observed in recently completed Phase II - III studies in a wide spectrum of tumors, including RCC, neuroendocrine tumors, tuberous sclerosis complex, SEGAs and angiomyolipomas, lymphoma and gastric, breast and hepatocellular cancers. These findings emphasize the importance of mTOR in diverse cancers and rare diseases and underscore the potential role for everolimus as an effective agent in multiple indications. © 2011 Informa UK, Ltd. |
| Keywords: | signal transduction; cancer chemotherapy; treatment outcome; treatment response; treatment failure; unclassified drug; overall survival; drug tolerability; fatigue; histopathology; neutropenia; review; sorafenib; bevacizumab; cisplatin; cytotoxic agent; placebo; sunitinib; cancer combination chemotherapy; diarrhea; drug dose comparison; drug efficacy; drug safety; liver cell carcinoma; monotherapy; nonhuman; side effect; solid tumor; drug targeting; pathophysiology; paclitaxel; cancer patient; cancer radiotherapy; glioma; neurosurgery; genetic analysis; anorexia; neoplasm; colorectal cancer; treatment indication; cell proliferation; biomarkers; biological marker; gastrointestinal stromal tumor; imatinib; disease association; drug inhibition; progression free survival; quality of life; drug eruption; infection; multiple cycle treatment; ovary cancer; pharmacodynamics; breast cancer; anemia; leukopenia; stomatitis; thrombocytopenia; aromatase inhibitor; lung cancer; hemoglobin blood level; waldenstroem macroglobulinemia; antineoplastic activity; drug structure; in vitro study; drug development; drug design; vasculotropin inhibitor; oncology; cancer research; renal cell carcinoma; kidney carcinoma; hodgkin disease; exemestane; protein tyrosine kinase inhibitor; temsirolimus; alanine aminotransferase blood level; asthenia; coughing; hyperglycemia; lymphocytopenia; neuroendocrine tumor; pneumonia; prostate cancer; drug induced headache; hematologic malignancy; nonhodgkin lymphoma; angiomyolipoma; colon cancer; mammalian target of rapamycin; lymphoma; tamoxifen; nausea and vomiting; glucose blood level; stomach cancer; immunomodulation; cholesterol blood level; triacylglycerol blood level; hyperbilirubinemia; octreotide; letrozole; drug bioavailability; optimal drug dose; drug blood level; graft rejection; hypercholesterolemia; drug dose titration; cancer classification; alpha2a interferon; kidney cancer; trastuzumab; navelbine; risk reduction; chronic lymphatic leukemia; astrocytoma; everolimus; lactate dehydrogenase blood level; rapamycin; hyperlipidemia; drug binding; drug stability; tuberous sclerosis; peripheral blood mononuclear cell; mtor; epidermal growth factor receptor kinase inhibitor; rare disease; randomized controlled trial (topic); drug solubility; clinical trial (topic); multicenter study (topic); ap 23753; ridaforolimus; restenosis; sinusitis; subependymal giant cell astrocytoma; tooth infection; viral bronchitis |
| Journal Title: | Expert Opinion on Drug Discovery |
| Volume: | 6 |
| Issue: | 3 |
| ISSN: | 1746-0441 |
| Publisher: | Informa Healthcare |
| Date Published: | 2011-03-01 |
| Start Page: | 323 |
| End Page: | 338 |
| Language: | English |
| DOI: | 10.1517/17460441.2011.558079 |
| PROVIDER: | scopus |
| PUBMED: | 22647206 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "Source: Scopus" |
