Resistance to Therapy
Gabriel Rivera1, Heather A Wakelee2
1Stanford University, Kaiser Permanente Fresno, Stanford, USA.
Abstract:
Identification of driver mutations in adenocarcinoma of the lung has revolutionized the treatment of this disease. It is now standard of care to look for activating mutations in epidermal growth factor receptor (EGFR), and translocations in anaplastic lymphoma kinase (ALK) or ROS1 in all newly diagnosed adenocarcinoma of the lung, and in many patients with squamous cell carcinoma as well. Recognition of multiple other lung cancer driver mutations has also expanded treatment options. Targeted treatments of these mutations lead to rapid and prolonged responses, but resistance inevitably develops. Until recently, traditional chemotherapy was the only alternative at that time, but better understanding of resistance mechanisms has lead to additional therapeutic options. These mechanisms of resistance and treatments are the focus of this chapter. Understanding of mechanisms of chemotherapy resistance is touched upon, along with a brief discussion of immune checkpoint inhibitors.
Insights
Targeted therapies for lung cancer, including EGFR, ALK, and ROS1 mutations, offer significant benefits but resistance develops. Understanding resistance mechanisms is key to developing new treatments beyond chemotherapy and immune checkpoint inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Lung adenocarcinoma treatment has been transformed by identifying driver mutations.
- Testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS1 alterations is standard for lung cancer.
- Numerous other lung cancer driver mutations have expanded therapeutic strategies.
Purpose of the Study:
- To review mechanisms of resistance to targeted lung cancer therapies.
- To discuss emerging treatment options for overcoming resistance.
- To briefly touch upon chemotherapy resistance and immune checkpoint inhibitors.
Main Methods:
- Literature review focusing on resistance mechanisms in lung cancer.
- Analysis of current and emerging therapeutic strategies.
- Discussion of underlying biological processes of resistance.
Main Results:
- Targeted treatments yield rapid, durable responses but are eventually overcome by resistance.
- Understanding resistance mechanisms enables the development of novel therapeutic approaches.
- Chemotherapy and immune checkpoint inhibitors represent alternative or complementary strategies.
Conclusions:
- Resistance to targeted lung cancer therapies is inevitable and necessitates continuous research.
- Advances in understanding resistance mechanisms are crucial for improving patient outcomes.
- A multi-faceted approach combining targeted therapy, chemotherapy, and immunotherapy is essential.
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