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Updated: Aug 25, 2025
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance
Adnin Ashrafi1, Zakia Akter1, Pouya Modareszadeh1
1Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Abstract:
Lung cancer is one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains a major obstacle to the effectiveness of long-term treatment, eventually leading to therapeutic insensitivity, poor progression-free survival, and disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations in the tumor microenvironment, and several other cellular and molecular alterations. A better understanding of these mechanisms is crucial for targeting factors involved in therapeutic resistance, establishing novel antitumor targets, and developing therapeutic strategies to resensitize cancer cells towards treatment. In this review, we summarize diverse mechanisms driving resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and promising strategies to help overcome this therapeutic resistance.
Insights
Lung cancer treatment resistance is a major challenge. Understanding resistance mechanisms is key to developing new strategies to resensitize cancer cells and improve patient survival rates.
Area of Science:
- Oncology
- Cancer Research
- Molecular Biology
Background:
- Lung cancer is a leading cause of cancer mortality globally, with a low 5-year survival rate.
- Current treatments (surgery, chemotherapy, radiation, targeted therapy, immunotherapy) face significant challenges due to therapeutic resistance.
- Therapeutic resistance leads to treatment insensitivity, poor progression-free survival, and disease relapse.
Purpose of the Study:
- To review diverse mechanisms driving resistance to various lung cancer treatments.
- To summarize promising strategies for overcoming therapeutic resistance in lung cancer.
- To highlight the importance of understanding resistance for developing novel antitumor targets.
Main Methods:
- Comprehensive literature review of mechanisms of therapeutic resistance in lung cancer.
- Analysis of genetic, epigenetic, and tumor microenvironment factors contributing to resistance.
- Synthesis of current and emerging strategies to overcome treatment resistance.
Main Results:
- Resistance mechanisms are multifaceted, involving genetic/epigenetic changes, drug efflux, hypoxia, and tumor microenvironment alterations.
- A deep understanding of these mechanisms is critical for effective treatment.
- Various strategies are being explored to resensitize lung cancer cells to therapy.
Conclusions:
- Overcoming therapeutic resistance is crucial for improving lung cancer patient outcomes.
- Targeting resistance mechanisms offers a promising avenue for novel treatment strategies.
- Further research into resistance pathways will facilitate the development of more effective lung cancer therapies.
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