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Side effects of anti-cancer molecular-targeted therapies (not monoclonal antibodies)
Gilberto de Castro1, Ahmad Awada
1Clinical Oncology Service, Radiology Department, InRad, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil.
Purpose Of Review:
Major advances have been achieved in the field of biologically based therapies for cancer in the last few years, and some of the recently approved 'molecular-targeted therapies' are now being used in daily clinical practice. We aim to review some aspects of the toxicity and safety of small-molecule anti-cancer molecular-targeted therapies, with some insights into the physiopathology and predictive factors of toxicity, its correlation with response, and how to prevent and overcome it.
Recent Findings:
As a whole, small-molecule molecular-targeted therapies are well tolerated. Their toxic profile is favorable, but during the drug development process some severe (sometimes lethal) toxicities have been observed, such as interstitial lung disease in patients treated with drugs targeting the epidermal growth factor receptor. Pharmacogenomic studies can help us to identify those patients with well characterized polymorphisms, and to define the best-tolerated and most effective treatments.
Summary:
Molecular-targeted therapies have a good toxicity profile in general; however, some patients are exquisitely sensitive to developing particular and severe toxicities related to these drugs.
Insights
Small-molecule molecular-targeted therapies for cancer generally have favorable toxicity profiles. However, some patients experience severe toxicities, necessitating personalized treatment approaches informed by pharmacogenomics.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Recent advancements in biologically based cancer therapies have led to the approval and clinical use of molecular-targeted therapies.
- Small-molecule molecular-targeted therapies represent a significant development in cancer treatment.
Purpose of the Study:
- To review the toxicity and safety of small-molecule anti-cancer molecular-targeted therapies.
- To explore the physiopathology, predictive factors, and management of toxicities associated with these therapies.
- To examine the correlation between toxicity and treatment response.
Main Methods:
- Literature review focusing on molecular-targeted therapies in oncology.
- Analysis of safety data and toxicity profiles from clinical studies.
- Exploration of pharmacogenomic data for predicting and managing toxicity.
Main Results:
- Small-molecule molecular-targeted therapies are generally well-tolerated with a favorable toxic profile.
- Severe toxicities, including interstitial lung disease (e.g., with EGFR inhibitors), have been observed.
- Pharmacogenomic studies offer potential for identifying susceptible patients and optimizing treatment.
Conclusions:
- Molecular-targeted therapies exhibit a generally good safety profile.
- Certain patients may exhibit heightened sensitivity to specific severe toxicities.
- Personalized medicine approaches, guided by pharmacogenomics, are crucial for optimizing safety and efficacy.
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