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…
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…
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 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 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 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…
Molecular Diagnostics of Myeloid Neoplasms
Myeloproliferative neoplasms Chronic myelogenous leukemia, BCR-ABL1-positive Chronic neutrophilic leukemia Polycythemia vera Primary myelofibrosis Essential thrombocythemia Chronic eosinophilic leukemia, NOS Mastocytosis Myeloproliferative neoplasm, unclassifiable Myeloid and lymphoid neoplasms with eosinophilia and…
Molecular Pathology and Diagnostics of Colorectal Cancer
Fig. 5.1 An example of a PTT from Ref. [136]. Eight representative samples from de novo CRCs (T1 → T8), with truncating mutations identified by sequencing analysis. A substantial amount of normal…
