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Oncology Drug Development Update Molecular Profiling Redefines The Nature Of Malignancy And Increases The Adoption Of Targeted Therapeutics
Identification of novel
cancer-related targets and pathways is redefining our understanding of the
nature of malignancy. Molecular profiling is prompting new, more detailed
classifications of malignancy enabling the development of
specific/personalized cancer therapies. Standard classifications involving
gross pathologic hallmarks such as stage and grade are now being further
augmented by data detailing the overexpression of oncogenes, silencing of
tumor suppressors and presence of mutant forms of relevant markers. In each
of these cases novel targeted agents and various combination strategies are
being investigated based on the specific molecular profiles of cancer
subtypes.
Molecular Profiling Improves Classification and Guides Treatment
In breast cancer, for example, classification has been extended to
include metastatic sites (bone, brain), expression of HEr2, and hormone
receptor status. A recently introduced classification is triple negative
(Er-, Pgr- and HEr2-) breast cancer, also known as basal-cell cancer. Other
classifications include inflammatory breast cancer and ductal carcinoma in
situ. Different treatment strategies are in development for each of these
tumor types. Similarly, most other malignancies are also undergoing
reclassification based on specific molecular profiles. Elucidation of the
role of Kras in the success or failure of EGFr inhibition in the treatment
of colorectal cancer exemplifies the recent remarkable achievements that
have been made based on molecular profiling. Authoritative cancer agencies
are taking notice. The National Comprehensive Cancer Network (NCCN) has
begun to incorporate diagnostic, prognostic and pharmacogenomic evaluations
in their updated treatment guidelines.
Targeted Agents in Combination are Entering Clinical Trials
The validated association of aggressive disease and the overexpression
of HEr2 in any type or stage of breast cancer have created a $4 billion
global market for trastuzumab (Herceptin; Genentech) in 2007. Still, nearly
50% of HEr2-positive patients do not respond to trastuzumab, and survival
benefits are transient, often lasting under a year. Furthermore, side
effects remain a significant problem. Despite these limitations,
trastuzumab is the standard of treatment for both early stage and advanced
or metastatic disease and is undergoing clinical trials in combination with
numerous approved or novel anticancer agents.
Hundreds of clinical trials are underway combining approved targeted
therapeutics with every applicable cytotoxic(s) with the goal of achieving
incremental benefits. The greater opportunity, however, may lie in
combining targeted therapeutics that address different points in one
pathway or interacting pathways involved in angiogenesis, metastasis, drug
resistance, and tumor growth and survival. This approach has entered the
clinic; recently initiated trials are testing combinations of approved
targeted therapeutics with each other. The full impact of combining target
agents, however, will not be measured until approved and novel agents are
combined in hundreds of different combinations for the treatment of
hundreds of specific cancer indications.
Future Oncology Series Details ErbB Pathway-targeted Therapeutics
To date, ErbB pathway abnormalities, which occur in a large number of
malignancies, have been the most extensively targeted. Currently, there are
7 approved agents targeting this pathway and over 620 clinical trials are
ongoing with these agents in various combinations, mostly with cytotoxic
agents but also with each other and with selected novel agents under
clinical development. In addition to the over 56 ErbB-targeted agents in
development (35 in current clinical trials), numerous molecular
markers/pathways are being recognized as contributing to the success or
failure of the ErbB pathway inhibitors.
New Medicine's Oncology KnowledgeBASE (nm|OK) is a Complete Knowledge
Environment in Drug Development in Cancer
Unlike standard drug databases, nm|OK residing at http://www.nmok.net,
is designed to specifically provide a fully realized environment reflecting
every aspect of drug development in oncology. nm|OK is an edited, inclusive
analysis of all aspects of oncology drug development worldwide, including
technologies, targets, companies, business affiliations, medical and
clinical developments, protocols and results of thousands of clinical
trials, and global markets, among others. Currently, nm|OK profiles over
2,000 anticancer agents/technologies in current development (over 4,000
drugs overall) or on the market, more than 1,200 targets implicated in
malignancy, and more than 2,000 companies developing/marketing products in
the oncology sector. Protocols, interim and final results are presented for
thousands of trials, searchable by both novel and approved agents in
monotherapy or combination therapy regiments. In addition, nm|OK describes
hundreds of diagnostic, prognostic, and theragnostic methodologies and
products as they relate to treatment candidate selection, evaluation of the
results of clinical trials, and early and accurate detection of disease.
New Medicine, Inc.
http://www.newmedinc.com
Oncologie de droguri de dezvoltare actualizare molecularã profilare redefineºte natura boli maligne ºi creºteri de la adoptarea orientate therapeutics - Oncology Drug Development Update Molecular Profiling Redefines The Nature Of Malignancy And Increases The Adoption Of Targeted Therapeutics - articole medicale engleza - startsanatate