Molecular Targeted Therapy in Oncology Focusing on DNA Repair Mechanisms

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• DNA repair mechanisms are crucial for cellular homeostasis; their malfunction causes mutations, cancer, and cell death.
• Defects in DNA repair pathways create specific vulnerabilities in cancer cells, exploitable for targeted therapies.
• Targeting the DNA damage response (DDR) presents a novel therapeutic strategy for patients with deficient DDR.

Purpose of the Study:

• To review the current state of DNA repair mechanisms as therapeutic targets in oncology.
• To explain treatment options targeting DNA repair deficiencies, specifically Mismatch Repair (MMR) and Homologous Recombination Repair (HRR).
• To highlight ongoing clinical trials exploring advanced treatments for dMMR and HRD patients.

Main Methods:

• Review of current literature on DNA repair mechanisms and their therapeutic implications.
• Analysis of targeted therapies including immunotherapy (checkpoint inhibitors - ICIs) and PARP inhibitors (PARPi).
• Discussion of clinical trials investigating treatments for deficient MMR (dMMR) and Homologous Recombination Deficiency (HRD) in solid tumors.

Main Results:

• MMR and HRR deficiencies are key targets for molecular therapies.
• ICI and PARPi drugs demonstrate efficacy in solid tumors with specific DNA repair defects.
• Numerous clinical trials are actively exploring enhanced treatment strategies for dMMR and HRD.

Conclusions:

• Exploiting DNA repair defects offers a promising avenue for improving anticancer treatment efficacy and patient outcomes.
• Targeted therapies based on DDR inhibition, including ICIs and PARPi, represent a significant advancement in cancer treatment.
• Further research and clinical trials are essential to optimize treatments for patients with deficient DNA repair mechanisms.