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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
Targeted cancer therapeutics
William N Hait1, Trevor W Hambley
1Division of Johnson and Johnson, Ortho Biotech Oncology Research and Development, Raritan, New Jersey 08869, USA. WHait@ITS.JNJ.COM
Abstract:
Targeted therapies can be defined as drugs developed against a specific target based on its important biological function in cancer. In contrast, nontargeted therapies are drugs identified by phenotypic screening of natural products or chemical libraries against established cancer cell lines or preclinical animal models without a priori knowledge of the target. Targeted therapies are designed to selectively inhibit a target that is abnormal in malignant compared with normal tissues; these drugs often affect proximal events in signaling pathways that drive abnormal growth and have relatively low toxicity. In contrast, nontargeted therapies affect proteins or nucleic acids that may or may not be abnormal in malignant compared with normal tissues; these drugs often target the downstream consequences of activated signaling pathways, e.g., DNA synthesis and microtubule assembly, and are toxic. Whereas targeted therapies are highly effective in selected hematopoietic malignancies, most have shown limited efficacy against complex solid tumors. In contrast, nontargeted drugs include some of the most effective yet most toxic drugs in the oncology pharmacopoeia. In the future, advances in genomics, proteomics, biology, biomarkers, chemistry, and protein engineering will coalesce to accelerate the development of increasingly selective and effective targeted therapies. Understanding the target in context will help identify biomarkers predictive of response. Finally, a detailed understanding of the target's structure and function will help anticipate and identify mechanism of drug resistance and help design drugs and combinations of drugs that retain activity.
Insights
Targeted cancer therapies attack specific cancer cell targets with lower toxicity, while nontargeted therapies affect broader cellular processes, often with higher toxicity. Future advances will enhance targeted therapy effectiveness, especially for solid tumors.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cancer therapies are broadly classified into targeted and nontargeted approaches.
- Targeted therapies are designed against specific molecular targets crucial for cancer cell function.
- Nontargeted therapies are identified through phenotypic screening and often affect fundamental cellular processes.
Purpose of the Study:
- To differentiate between targeted and nontargeted cancer therapies.
- To discuss the efficacy, toxicity, and applications of each therapy type.
- To explore future directions in the development of targeted cancer therapies.
Main Methods:
- Review of existing literature and definitions of targeted and nontargeted therapies.
- Comparative analysis of their mechanisms of action, toxicity profiles, and clinical efficacy.
- Discussion of future trends based on advancements in related scientific fields.
Main Results:
- Targeted therapies offer selective inhibition of cancer-specific targets with generally lower toxicity.
- Nontargeted therapies, while effective, often exhibit significant toxicity due to their broader mechanisms.
- Targeted therapies show high efficacy in hematologic malignancies but limited success in solid tumors, unlike nontargeted drugs.
- Nontargeted drugs represent some of the most effective yet toxic agents in cancer treatment.
Conclusions:
- Future advancements in genomics, proteomics, and drug design will drive the development of more selective and effective targeted therapies.
- Identifying predictive biomarkers and understanding drug resistance mechanisms are crucial for optimizing targeted therapy outcomes.
- A comprehensive understanding of drug targets is essential for designing effective combination therapies and overcoming resistance.
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