Targeted Therapy in Non-Small Cell Lung Cancer

Introduction

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. However, advancements in medical research have led to the development of targeted therapies, offering new hope for patients. Lung cancers are divided into non-small cell and small cell lung cancers. This blog delves into an overview of targeted therapy used in non-small cell lung cancer.

What is Targeted Therapy?

Targeted therapy is a type of cancer treatment that uses drugs designed to specifically identify and attack cancer cells while minimizing damage to normal cells. Unlike traditional chemotherapy, which affects all rapidly dividing cells, targeted therapy focuses on specific cancer-associated molecular targets.

How Does It Work?

Targeted therapies interfere with specific molecules involved in tumor growth and progression. These therapies can block the growth signals of cancer cells, prevent the formation of new blood vessels that nourish tumors, or directly induce cancer cell death.

Testing For Molecular Targets

The advances in the management of lung cancer have been made possible due to improvements in diagnostic techniques. Molecular testing with next-generation sequencing has revolutionized the treatment of non-small cell lung cancers. It has identified several new mutations that can be targeted by novel medications. Around 10 driver mutations have been identified using these techniques. 

Programmed Death-Ligand 1 (PDL 1) tests are used in the context of immunotherapy to determine the expression levels of the PD-L1 protein on the surface of cancer cells and immune cells within a tumor. These tests are important for predicting how well a patient might respond to certain immunotherapy drugs, particularly immune checkpoint inhibitors.

These tests, initially, were expensive, but now with more customised and Indigenous panels, it has become more affordable. Hence it has become an indispensable part in the management of non-small cell lung cancers.

Types of Targeted Therapy in Non-Small Cell Lung Cancer

1. Tyrosine Kinase Inhibitors (TKIs)

Epidermal Growth Factor Receptor Inhibitors (EGFR) and Anaplastic Lymphoma Kinase Inhibitors (ALK) are among the common mutations occurring in lung cancer that can be targeted. Other targets include ROS1, RET, MET, BRAF, KRAS, and NTRK. 

• EGFR Inhibitors: EGFR mutations are common in non-small cell lung cancer (NSCLC). Drugs like erlotinib, gefitinib, and Osimertinib target these mutations, inhibiting the signaling pathways that promote cancer cell growth.
• ALK Inhibitors: ALK rearrangements occur in a subset of NSCLC. ALK inhibitors such as crizotinib, ceritinib, and alectinib are designed to block the abnormal ALK protein, thus slowing down or stopping cancer growth.

2. Immune Checkpoint Inhibitors

PD-1/PD-L1 Inhibitors are a type of targeted therapy that targets the immune system of cancer cells. Drugs like pembrolizumab and nivolumab block the interaction between PD-1 on T-cells and PD-L1 on cancer cells thereby enhancing the immune system's ability to attack cancer cells. These can be used either as a single agent or along with chemotherapy to potentiate its effect based on the score obtained on PDL 1 testing. 

• Benefits of Targeted Therapy

• Precision: Targeted therapy specifically attacks cancer cells, leading to fewer side effects compared to traditional chemotherapy.
• Efficacy: Patients with specific genetic mutations often respond well to targeted therapies.
• Quality of Life: The reduced side effects and improved effectiveness contribute to a better quality of life for patients.
• Challenges and Limitations
• Resistance: Over time, cancer cells can develop resistance to targeted therapies, necessitating alternative treatments or combination therapies.
• Side Effects: While generally less than chemotherapy, targeted therapies can still cause side effects such as skin rash, diarrhoea, and liver toxicity.
• Cost: Targeted therapies can be expensive, and access to these treatments may be limited by insurance coverage and availability. However, the cost of these medications has come down significantly in the past decade which has made it more affordable. 

Conclusion

Targeted therapy represents a significant advancement in the treatment of lung cancer, offering a more personalized approach to cancer care. As research continues to evolve, the hope is that newer targeted therapies that are more effective and which target newer mutations will be developed, leading to improved survival rates and quality of life for lung cancer patients.