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Combination Therapies and Personalized Medicine02:50

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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
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From osimertinib to preemptive combinations.

Mikhail V Blagosklonny1

  • 1Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Oncotarget
|March 18, 2024
PubMed
Summary
This summary is machine-generated.

First-line osimertinib improves median progression-free survival (PFS) for EGFR-mutant lung cancer but can harm some patients. Preemptive combination therapy offers a potential solution to increase PFS for most patients without harm.

Keywords:
EGFRNSCLCafatinibcapmatinibgefitiniblung cancerresistance

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Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) mutations drive lung cancer.
  • Osimertinib is a first-line treatment for EGFR-mutant lung cancer, extending median progression-free survival (PFS).
  • However, a subset of patients experiences reduced PFS with osimertinib compared to earlier treatments.

Purpose of the Study:

  • To evaluate the potential harm of first-line osimertinib in a subset of EGFR-mutant lung cancer patients.
  • To propose preemptive combination (PC) therapies to improve PFS and avoid harm.
  • To explore PCs for MET-driven lung cancer.

Main Methods:

  • Comparative analysis of PFS data for osimertinib versus first-generation TKIs.
  • Conceptualization of preemptive combination therapies.
  • Exploration of treatment strategies for MET-driven lung cancer.

Main Results:

  • First-line osimertinib extends median PFS but reduces individual PFS in 15-20% of patients.
  • A comprehensive PC of osimertinib, afatinib/gefitinib, and capmatinib could significantly increase PFS for 80% of patients.
  • The proposed PCs aim to maximize PFS benefits without causing harm.

Conclusions:

  • Osimertinib is essential for first-line treatment due to overall median PFS gains, despite potential individual harm.
  • Preemptive combination therapy represents a promising strategy to enhance treatment efficacy and patient outcomes in EGFR-mutant and MET-driven lung cancer.
  • Further research into comprehensive preemptive combinations is warranted.