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Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Cardiovascular effects of EGFR (epidermal growth factor receptor) monoclonal antibodies
Preeti Chaudhary1, Ajeet Gajra
1Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Abstract:
Molecular inhibition of the epidermal growth factor receptor (EGFR) is a promising anticancer strategy and monoclonal antibodies (mAbs) to EGFR are undergoing extensive evaluation in preclinical and clinical trials. EGFR is frequently over expressed in many types of human malignancy and may be associated with prognosis, disease stage and survival. Therefore, EGFR represents an attractive target for cancer therapy. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Although rare, cardiac toxicity is a significant complication associated with cetuximab and the clinical spectrum of these toxicities can range from subclinical abnormalities to being catastrophic, life-threatening and sometimes fatal events. This review aims to highlight an important albeit inadequately studied toxicity related to EGFR mAbs. We shall review preclinical and clinical literature to ascertain the etiology, incidence and management of cardiovascular complications of monoclonal antibodies to EGFR. As the potential clinical applications for these agents increase, clinicians using these agents need to remain vigilant regarding cardiovascular complications, especially in view of an aging cancer population.
Insights
Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) show promise in cancer treatment but can cause rare, severe cardiac toxicity. Vigilance is crucial for clinicians managing patients receiving these EGFR inhibitors.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) is a key target in cancer therapy.
- EGFR overexpression is linked to poor prognosis in various malignancies.
- Monoclonal antibodies (mAbs) targeting EGFR are under extensive clinical evaluation.
Purpose of the Study:
- To review the etiology, incidence, and management of cardiovascular complications associated with EGFR mAbs.
- To highlight the understudied cardiac toxicities of EGFR-targeted therapies.
- To inform clinicians about potential cardiac risks in patients receiving EGFR inhibitors.
Main Methods:
- Review of preclinical and clinical literature.
- Analysis of data on cardiovascular complications of EGFR mAbs.
- Synthesis of information on the clinical spectrum of cardiac toxicities.
Main Results:
- EGFR mAbs, such as cetuximab and panitumumab, inhibit EGFR signaling.
- Cardiac toxicity is a rare but significant complication of EGFR mAbs.
- These toxicities can range from subclinical to life-threatening events.
Conclusions:
- Clinicians must remain vigilant for cardiovascular complications in patients treated with EGFR mAbs.
- An aging cancer population may be particularly susceptible to these cardiac toxicities.
- Further research is needed to fully understand and manage these adverse events.
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