Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt pathway is heavily deregulated in breast cancer, the application of mTOR inhibitors in breast cancer patients seems warranted. This is the first systematic review according to PRISMA guidelines to synthesize all available data of mTOR inhibitors in all subcategories of breast cancer. The search strategy retrieved 16 studies evaluating everolimus (1492 patients), seven studies examining temsirolimus (1245 patients), one study evaluating sirolimus (400 patients) and two studies evaluating MKC-1 (60 patients). The Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study has marked a turning point in the evaluation of everolimus in the treatment of estrogen receptor positive breast cancer. Given the positive results, everolimus has entered NCCN 2012 guidelines, and its approval of its combination with exemestane by FDA and EMA is imminent. In addition, the promising antitumor activity and long-term disease control further suggest that mTOR inhibition with everolimus may provide an avenue for achieving long-lasting benefit from trastuzumab-based therapy in HER2-positive patients. Regarding temsirolimus, it seems that the agent may play, in the future, a role in the treatment of metastatic breast cancer; importantly, however, there is an unmet need to find its optimal target subpopulation.
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PMID:mTOR inhibitors in breast cancer: a systematic review. 2296

Metastasis is associated with poor prognosis in cancers. Exosomes, which are packed with RNA and proteins and are released in all biological fluids, are emerging as an important mediator of intercellular communication. However, the function of exosomes remains poorly understood in cancer metastasis. Here, we demonstrate that exosomes isolated by size-exclusion chromatography from a highly metastatic human oral cancer cell line, HOC313-LM, induced cell growth through the activation of ERK and AKT as well as promoted cell motility of the poorly metastatic cancer cell line HOC313-P. MicroRNA (miRNA) array analysis identified two oncogenic miRNAs, miR-342-3p and miR-1246, that were highly expressed in exosomes. These miRNAs were transferred to poorly metastatic cells by exosomes, which resulted in increased cell motility and invasive ability. Moreover, miR-1246 increased cell motility by directly targeting DENN/MADD Domain Containing 2D (DENND2D). Taken together, our findings support the metastatic role of exosomes and exosomal miRNAs, which highlights their potential for applications in miRNA-based therapeutics.
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PMID:Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma. 2792 18