New cancer therapeutics: target-specific in, cytotoxics out?
The International Conference on Molecular Targets and Therapeutics, jointly sponsored by the American Association for Cancer Research (AACR), National Cancer Institute (NCI) and European Organization for Research and Treatment of Cancer (EORTC), was held in Boston on November 17-21, 2003. It offered updates of the latest developments and emerging trends in anti-cancer research. One of the most exciting areas was the development of molecular target-specific therapeutics that have the potential to maximize therapeutic benefit while minimizing toxicity to normal cells. Signifying the coming of age of tumour-specific targets and agents was the recurring theme, to urgently develop and validate biomarker assays as surrogate endpoints; both for showing that targeted agents act as expected and for providing proof of concept in the scientific rationale of new agents. Given the dominance of protein tyrosine kinase inhibitors in small-molecule drug design, a strong case was made for the implementation of phospho-proteomics or signal transduction signatures and pharmaco-proteomics or chemotherapeutic scans in phase I/II trials--or for the future "Nanolab", eloquently described by Leroy Hood. However, molecular targeted agents-other than imanitib (Gleevec)--have yet to enter broad clinical use and several presentations described efforts for improving classical (cytotoxic) chemotherapeutic agents by targeting them selectively to tumour cells.
Broxterman
Henk J
HJ
Department of Medical Oncology, VU University Medical Center, BR 232, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. h.broxterman@vumc.nl
Georgopapadakou
Nafsika H
NH
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000077156:Gefitinib; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D040901:Proteomics / Q000379:methods*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use; D000077210:Sunitinib
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D011758:Pyrroles; D011799:Quinazolines; C015482:protein kinase modulator; C116890:Semaxinib; D000077156:Gefitinib; D000077210:Sunitinib