[Modern Approaches to Anti-EGFR Therapy]
E V Dudkina1, A I Nadyrova1,2, S A Luginskaya1
1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420008 Russia.
Abstract:
The epidermal growth factor receptor (EGFR) is among the research subjects of most interest and remains genuinely attractive due to its key role in regulating the main conserved signaling pathways responsible for cell growth, survival, and proliferation. Dysregulation of the signaling pathways leads to cell malignant transformation, tumor progression, and metastasis. Therefore, EGFR is considered as one of the main targets for anticancer drug development. Although several generations of novel anti-EGFR drugs have been successfully developed, acquisition of drug resistance and the mutation status of the downstream effector protein KRAS significantly reduce the tumor response to therapy. The review focuses on the current approaches to anti-EGFR therapy. Drugs designed to block the EGFR-mediated signaling are described, including monoclonal antibodies, tyrosine kinase inhibitors, and immunotoxins. Mechanisms of acquired resistance to anti-EGFR therapy are discussed, and combination treatment strategies are proposed to improve the efficacy of the available drugs. Finally, promising antitumor agents, including ribonucleases (RNases) of various origins, are considered.
Insights
Targeting epidermal growth factor receptor (EGFR) is crucial for cancer therapy. This review explores anti-EGFR drugs, resistance mechanisms, and novel combination strategies, including ribonucleases (RNases), to enhance antitumor efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) signaling is vital for cell growth, survival, and proliferation.
- Dysregulation of EGFR pathways drives cancer development, progression, and metastasis.
- EGFR is a primary target for developing anticancer drugs.
Purpose of the Study:
- To review current anti-EGFR therapies and their limitations.
- To discuss mechanisms of acquired resistance to EGFR-targeted drugs.
- To explore combination strategies and novel agents for improved cancer treatment.
Main Methods:
- Review of existing literature on anti-EGFR therapies.
- Analysis of drug resistance mechanisms in EGFR-targeted cancer treatment.
- Evaluation of combination treatment strategies and emerging agents like RNases.
Main Results:
- Several generations of anti-EGFR drugs (monoclonal antibodies, TKIs, immunotoxins) have been developed.
- Acquired resistance and KRAS mutations limit therapeutic response.
- Combination therapies and agents like RNases show promise for overcoming resistance.
Conclusions:
- EGFR-targeted therapies are essential but face challenges from drug resistance.
- Combination strategies are crucial for enhancing the efficacy of anti-EGFR treatments.
- Ribonucleases (RNases) represent a promising class of novel antitumor agents.
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