Introduction: Adrenocortical cancer (ACC) is a rare disease with very poor outcome. ACC responds poorly to standard chemotherapy. Mitotane, used as adjuvant therapy to surgery, prolongs recurrence-free survival, but the response is limited to 23% of patients and resistance occurs in the majority of patients (1). There is no curative therapy for ACC. Pre-clinical studies have shown involvement of both IGF-2/IGF-1R and Akt/mTOR pathways in ACC, and IGF-1R and mTOR inhibitors inhibited cell proliferation of human adrenocortical carcinoma cell lines in vitro (2,3,4).
Aim(s): To evaluate the therapeutic effects of everolimus (RAD001, Novartis) in ACC.
Materials and methods: A female patient, diagnosed incidentally with a non-functioning right ACC, underwent laparoscopic resection. The histology confirmed malignancy. Referred to our department, the patient was started on mitotane. Two months later, she developed a single liver metastasis which was ablated with radiofrequency (RFA) six months after resection of the primary lesion. Subsequent imaging did not show new lesions or local recurrence. However, one year after resection of the primary lesion, she developed three new liver metastases and a large retroaortocaval lymph node. The patient refused standard chemotherapy. A low neutrophil count and raised gamma GT related to mitotane precluded entry to an experimental phase I clinical trial with an angiogenesis inhibitor. She received treatment instead with a selective IGF-1R inhibitor, OSI906 (OSI Pharmaceuticals Inc, NY) elsewhere (phase I trial, 150 mg twice daily), but showed progression and this was stopped. She was then treated with everolimus (RAD001) 10 mg daily.
Conference: 7th Annual ENETS Conference (2010)
Presenting Author: Dr Maria Gueorguiev
To read results and conclusion, please login ...
Further abstracts you may be interested in
Introduction: Medullary thyroid carcinoma (MTC) accounts for about 5-10% of all thyroid cancers, and while disease localized to the thyroid can be cured by surgery, there is no effective treatment for disseminated MTC. Constitutive activation of the RET proto-oncogene is implicated in familial and a proportion of sporadic cases, and up-regulates the AKT/PI3-kinase/mTOR signal transduction pathway. Recent studies have shown that the inhibitor of mTOR, everolimus (RAD001, Novartis, Basel), can inhibit the proliferation of the TT cell line and human MTC tumor cells in vitro. Clinically, everolimus has been shown to attenuate the progression of some gastrointestinal neuroendocrine tumors, but its clinical use in MTC has not yet been evaluated.
Conference: 7th Annual ENETS Conference (2010)
Presenting Author: Dr Maralyn R Druce
Introduction: Torin1, a new mTOR inhibitor that globally inhibits both mTORC1 and mTORC2, seems to impair cell growth and proliferation to a greater degree than rapamycin; its effects in NET cells are unknown.
Conference: 8th Annual ENETS Conference (2011)
Presenting Author: Dr. Simona Grozinsky-Glasberg
Introduction: The mammalian target of rapamycin (mTOR) is a protein kinase involved in the control of cancer cell metabolism, growth and proliferation. The mTOR pathway has attracted broad scientific and clinical interest, particularly in light of the ongoing clinical cancer trials with mTOR inhibitors in pts with neuroendocrine tumors (NETs). To identify the best candidates for treatment with mTOR inhibitors is challenging.
Conference: 10th Annual ENETS Conference (2013)
Category: Epidemiology/Natural history/Prognosis - Registries, nationwide and regional surveys
Presenting Author: Concetta Sciammarella
Introduction: Most patients with neuroendocrine tumors (NETs) require systemic treatment, often with a limited therapeutic effect. RAD001 and Torin1 are mTOR inhibitors (mTORi) known to suppress cell proliferation in NETs. However, cancer cells may use mTORi-induced autophagy to escape the anti-proliferative effect and to prolong cell survival. Chloroquine (CQ) and hydroxychloroquine (HCQ) inhibit autophagy.
Conference: 11th Annual ENETS Conference (2014)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: Dr. Simona Glasberg
Introduction: It has been demonstrated that mTOR inhibitors have potent anti-proliferative effects in a human Medullary Thyroid Carcinoma (MTC) cell line. We here explore the possible role of mTOR inhibitors, Everolimus and BEZ235 (which also inhibits the PI3K pathway) on the effects of Insulin-like Growth Factor-1 (IGF-1) in human MTC primary cultures.
Conference: 9th Annual ENETS Conference (2012)
Presenting Author: Mrs. Mariella Minoia