title: Targeting intracellular signal transduction. A new paradigm for a brave new world of molecularly targeted therapeutics.
abstract: Significant advances in the field of molecular biology over the past decade have led to a new era in cancer therapeutics, with an explosion of rationally designed therapeutic strategies directed against selective molecular targets. The complex array of aberrant signal transduction proteins involved in carcinogenesis has been the focus of target-based anticancer agents. Inhibitors of intracellular signal transduction represent a unique approach in that they inhibit critical downstream regulatory proteins, which are vital to the process of cellular communication. Although these agents are in early-phase evaluations, the preliminary data suggest that they are well tolerated and capable of target inhibition in surrogate and tumor tissue. Although the primary therapeutic benefit of these agents is expected to be decreased tumor growth, evidence suggests that objective tumor responses may also be achieved. There are many unresolved questions pertaining to the development of this class of compounds, including selection of optimal dose and schedule, determination of relevant endpoints, methods for target validation, and strategies for combination with cytotoxic agents. However, despite the numerous unresolved issues, the emergence of this class of compounds has resulted in an undeniable impact on the present and future of cancer therapeutics.
authors.affiliation: Division of Hematology-Medical Oncology, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Muralidhar
authors.initials: M
authors.lastname: Beeram
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D020319:Oligodeoxyribonucleotides, Antisense / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D000077157:Sorafenib; D013873:Thionucleotides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: C120227:2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide; D000970:Antineoplastic Agents; D001549:Benzamides; D001557:Benzenesulfonates; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010671:Phenylurea Compounds; D011725:Pyridines; D013873:Thionucleotides; D009536:Niacinamide; C099587:ISIS 5132; D000077157:Sorafenib; D019908:Proto-Oncogene Proteins c-raf; D020929:Mitogen-Activated Protein Kinase Kinases