Irinotecan the extracellular domain of EGFR and block ligand

With our greater understanding of the underlying molecular mecha- nisms of oncogenic transformation and tumorigenic- ity, we have gained a deeper appreciation for the inherent heterogeneity that exists within individual cancer types or histologies. Identifying molecular biomarkers that can be used to identify those patient subsets most likely to benefit from a specific drug has become a major goal in this new era of personalized or tailored therapy. In addition to tumor heterogene- ity, we have also gained an understanding of the Irinotecan naling plasticity that exists within tumor cells, allow- ing tumors to circumvent a targeted agent through either the acquisition of a drug-resistance mutation or the activation of an alternate signaling pathway to maintain tumor-cell growth and survival.

This has emphasized the importance of translational research to enable personalized anticancer therapeutic strate- gies aimed at delivering the right drug(s) to the right patients at the right time and with the right dose. Many innovations for molecularly targeted Nilotinib anticancer therapeutics have been driven by collaborative efforts between pharmaceutical companies and academic researchers. This review will emphasize the contin- ued need for collaborative industry-academia efforts, which can synergize in drug discovery and develop- ment. Four examples will be highlighted –cetuximab, trastuzumab, imatinib and dasatinib, and OSI- 906 –where efforts from both industry and aca- demic scientists synergized to enable drug-discovery achievements and the delivery of anticancer Many innovations for molecularly targeted anticancer therapeutics have been driven by collaborative efforts between pharmaceutical companies and academic researchers. This review will emphasize the continued need for collaborative industry-academia efforts, which can synergize in drug discovery and development. therapeutics to the clinic. These examples provide a model for future collaborative efforts.

DOI:0.00/MSJ Historical Roles of Academia and Industry in Drug Discovery and Irinotecan 97682-44-5 Development. Abbreviations: ID, identify; IND, Investigational New Drug Application. Basic research, publications, genetic models, cell models Launch, marketing, sales Commercialize Phase I, Phase II, Phase III Clinical Studies Candidate development, toxicology, pharmacology, process chemistry, define efficacy, ID biomarkers Medicinal chemistry, molecular modeling, refine potency, refine selectivity, refine pharmacology Assay development, compound libraries, virtual libraries, screening, rational design Pre-IND Studies Lead Optimization Lead Identification.

Academia Industry Activities Table . Target Validation Target Identification Basic research, publications, databases X X 360 DEVELOPMENT OF CETUXIMAB E. B UCK ET AL .: P URSUIT of P ERSONALIZED A NTICANCER T HERAPY with irinotecan for the treatment order Irinotecan of patients with EGFR-expressing, irinotecan-refractory CRC. 4 Academic research over the past 4 decades has shown that inappropriate or overactive signaling by the epi- dermal growth factor receptor (EGFR) is an important contributor to specific cancers, especially non –small- cell lung cancer (NSCLC), squamous cell cancer of the head and neck (SCCHN), and colorectal can- cer (CRC). Many tumor cell lines overexpress EGFR and/or overexpress the ligands for EGFR. Nonma- lignant cells ectopically overexpressing EGFR can be oncogenically transformed. .

3 Neutralizing antibodies that bind to the extracellular domain of EGFR and block ligand pathogen  binding are potent inhibitors of prolif- eration of tumor cell lines overexpressing EGFR. 3 – 5 Subsets of several cancer types, including NSCLC and SCCHN, overexpress EGFR. ,3 To investigate the role of EGFR in human cancers and whether targeting EGFR offered a strategy for therapeutic intervention, John Mendelsohn and his colleagues in academia developed several monoclonal antibodies against the extracellular domain of EGFR. 5 Some of these EGFR-targeted monoclonal antibo

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