Fig. 12.1 The PI3K pathway and associated inhibitor classes. Schematic representation of the PI3K/Akt/mTOR pathway (red) and the MAPK pathway (blue) including recognized points of crosstalk between the respective cascades….
Fig. 10.1 Oncogenic activation of mTOR may be related to multiple oncogenic activations, mutations of major anti-oncogenes as well as microenvironment-dependent parameters such as hypoxia and nutrient depletion Knowing how…
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…
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…
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…
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…
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…
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…
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…
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…
