The PI3K-mTOR Pathway
Fig. 2.1 mTOR signaling pathway (detailed in text) 2.2.1.1 mTORC1 mTORC1 includes two unique binding partners: regulatory associated protein of mTOR (Raptor), which recognizes mTOR substrates through their TOR Signaling…
ONCOLOGY
New Indications of mTOR Inhibitors in Rare Tumors
Clinical characteristic Diagnosis Major features Facial angiofibromas or forehead plaque Definite TSC: Either 2 major features or 1 major features plus 2 minor features Probable TSC: One major plus 1…
mTOR, Aging, and Cancer: A Dangerous Link
Fig. 13.1 mTOR complex 1 (mTORC1) signaling aging, longevity, and cancer. (a) Indicated above are stimuli that mTORC1 integrates in the execution of its cell autonomous functions. In a replete…
Potential Future Indication of Rapamycin Analogs for the Treatment of Solid Tumors
Agent Phase Clinical trial no. Number of patients Objective response rate (ORR, %) Progression-free survival (PFS) Overall survival (OS) Reference Temsirolimus 2 NCT00087074 41 5 2 months – median time…
Targeting mTOR: A Little Bit of History and a Large Future
Fig. 1.1 Chemical structure of rapamycin and rapalogs. Rapalogs have the indicated O-substitutions at the C-40 position of rapamycin (red circle) Temsirolimus, formerly known as CCI-779; Torcel®, Wyeth Pharmaceuticals, now…
The Role of PI3K/AKT/mTOR Inhibitors in the Treatment of Hematological Malignancies
Drug Target Stage of development and indications Company mTOR Sirolimus (rapamycin) mTOR Approved for renal transplant, phase II/III trials for MM, NHL Pfizer Temsirolimus (CCI779) mTOR Approved for RCC and…
The Role of mTOR Inhibitors in Neuroendocrine Tumors
Pathway alteration Incidence Tumor type References mTOR overexpression 6/9 (67 %) pNET Shida et al. [11] Mutations in PTEN, TSC2, PIK3CA 10/68 (15 %) pNET Jiao et al. [12] Akt…
The Role of mTOR Inhibitors in Breast Cancer
Patient population N Design Treatment arms Stratification factors Endpoints Results BOLERO-1 HER2+ ABC. First line 719 Randomization 2:1 Everolimus or placebo 10 mg/day + paclitaxel 80 mg/m2 days 1, 8, 15 + trastuzumab…
The Evolving Role of Mammalian Target of Rapamycin (mTOR) Inhibitors in Renal Cell Carcinoma
1. Serum LDH > 1.5 times the upper limit of normal 2. Hemoglobin level < lowest limit of normal 3. Corrected serum calcium level > 10 mg/dL (2.5 mmol/L) 4. Interval of less than 1 year…
Molecular Pathology and Diagnostics of Childhood Tumors
Chromosomal defect Childhood tumor 1p del, 1p32-p36 del, double minutes Neuroblastoma 11p13 del, trisomy 18 Wilms’ tumor 13q14 del Retinoblastoma Osteosarcoma Trisomy 21 (Down syndrome) Leukemia Monosomy 7 Leukemia and…
