The Next Step Involves Combining the 350+ Targeted Drugs on the Market and in Clinical Development with Each Other to Block Key Pathways to Combat Drug Resistance, Enhance Anticancer Effects, and Expand the Markets for
LAKE FOREST, Calif., Feb. 19 /PRNewswire/ -- 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. A series of reports (http://www.newmedinc.com/futonc/sample.pdf) on currently approved therapeutics as well as those in development targeting the ErbB pathway, including EGFr and HEr2 inhibitors, published by Future Oncology (http://www.newmedinc.com), highlights the contribution of molecular profiling in the characterization of cancer and its treatment.
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,
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2,000 anticancer agents/technologies in current development (over 4,000
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Contact us for an online demonstration of nm|OK.
Contact: Katie Siafaca
New Medicine, Inc.
Tel: (949) 830-0448; Fax: (949) 830-0887
|SOURCE New Medicine, Inc.|
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