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Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
New cancer therapeutics: target-specific in, cytotoxics out?
Henk J Broxterman1, Nafsika H Georgopapadakou
1Department of Medical Oncology, VU University Medical Center, BR 232, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. h.broxterman@vumc.nl
Abstract:
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.
Insights
The International Conference on Molecular Targets and Therapeutics highlighted advances in anti-cancer research, focusing on molecularly targeted therapies. Key themes included validating biomarker assays and integrating proteomics into clinical trials for better cancer treatment.
Area of Science:
- Oncology and Molecular Therapeutics
- Cancer Research
- Pharmacology
Background:
- The International Conference on Molecular Targets and Therapeutics (2003) convened leading researchers in anti-cancer drug development.
- Focus on molecularly targeted therapeutics aimed at maximizing efficacy and minimizing toxicity.
Framework:
- Urgent need for biomarker assay validation as surrogate endpoints for targeted agents.
- Demonstrating target engagement and proof of concept for novel anti-cancer drugs.
Implementation:
- Emphasis on phospho-proteomics and pharmaco-proteomics in early-phase clinical trials.
- Exploration of advanced concepts like the "Nanolab" for future drug development.
Implications:
- Molecularly targeted agents, beyond imatinib (Gleevec), require further clinical validation for broad use.
- Ongoing efforts to enhance classical cytotoxic chemotherapies through targeted delivery to tumor cells.
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