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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 Therapies
Claire Elizabeth Powers Smith1, Vinayak Prasad2
1Boston University School of Medicine, Boston, MA, USA.
Abstract:
Targeted cancer therapies involve chemotherapeutic agents that attack, directly or indirectly, a specific genetic biomarker found in a given cancer. Targeted oncology includes monoclonal antibodies, small molecule inhibitors, antibody-drug conjugates, and immunotherapy. For example, the monoclonal antibodies trastuzumab and pertuzumab target human epidermal growth factor receptor 2 (HER2) and are used when treating HER2-positive breast cancer. Although targeted oncology has improved survival by years for some incurable cancers such as metastatic breast and lung cancer, as few as 8% of patients with advanced cancer qualify for targeted oncology medications, and even fewer benefit. Other limitations include serious adverse events, illustrated by a 20% to 30% rate of heart attack, stroke, or peripheral vascular events among patients taking ponatinib, which is used in treating chronic myelogenous leukemia. Immune checkpoint inhibitor therapy-related adverse effects such as hypothyroidism are common, and more severe adverse events such as colitis and pneumonitis can be fatal and require immediate intervention. Drug interactions with widely prescribed medications such as antacids and warfarin are common. Additionally, financial toxicities are a problem for patients with cancer who are using costly targeted therapies. Future directions for targeted oncology include tumor-agnostic drugs, which target a given mutation and could be used in treating cancers from multiple organ types. An overview of indications, mechanism of action, and toxicities of targeted cancer therapies is offered here.
Insights
Targeted cancer therapies offer improved survival but have limited patient eligibility and significant adverse events. Future directions include tumor-agnostic drugs for broader application.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Targeted cancer therapies utilize agents like monoclonal antibodies and small molecule inhibitors to attack specific genetic biomarkers.
- Examples include trastuzumab and pertuzumab for HER2-positive breast cancer, improving survival for some advanced cancers.
Purpose of the Study:
- To provide an overview of targeted cancer therapies, including their indications, mechanisms of action, and associated toxicities.
- To highlight the limitations and future directions in the field of targeted oncology.
Main Methods:
- Review of current literature on targeted cancer therapies.
- Analysis of indications, mechanisms of action, and adverse events.
- Discussion of limitations such as patient eligibility, adverse events, drug interactions, and financial toxicity.
Main Results:
- Targeted therapies have improved survival for certain cancers but benefit a small percentage of advanced cancer patients (as low as 8%).
- Significant adverse events, including cardiovascular events (20-30% with ponatinib) and immune-related toxicities (hypothyroidism, colitis, pneumonitis), are common.
- Drug interactions and high costs present additional challenges.
Conclusions:
- Despite advancements, targeted oncology faces challenges in patient selection, toxicity management, and accessibility.
- Future research focuses on tumor-agnostic therapies targeting specific mutations for broader cancer treatment applicability.
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