Research and innovation in the development of everolimus for oncology.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Novartis Pharmaceuticals, Inc., 180 Park Avenue, Florham Park, NJ 07932, USA  +1 862 778 7218 ;  david.lebwohl@novartis.com.
David
D
Lebwohl
George
G
Thomas
Heidi A
HA
Lane
Terence
T
O'Reilly
Bernard
B
Escudier
James C
JC
Yao
Marianne
M
Pavel
David
D
Franz
William
W
Berg
Jean-Francois
JF
Baladi
Jubilee
J
Stewart
Robert J
RJ
Motzer