Question

Molecular targeted therapy in advanced non-small-cell lung cancer.

Hint:

Molecular targeted therapies, such as EGFR inhibitors and ALK inhibitors, offer personalized treatment for advanced NSCLC based on specific genetic mutations, leading to better outcomes with fewer side effects.

Answer 1

Step 1: Introduction to Molecular Targeted Therapy in Advanced Non-Small-Cell Lung Cancer (NSCLC).
Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Molecular targeted therapies are a newer class of treatments that target specific molecular changes within cancer cells, which are responsible for cancer growth and progression. These therapies are typically used in advanced stages of NSCLC, particularly when the cancer is metastatic or when chemotherapy is no longer effective. Step 2: Types of Molecular Targeted Therapies in NSCLC.
(1) Epidermal Growth Factor Receptor (EGFR) Inhibitors:
- EGFR is a receptor that is often overexpressed in NSCLC cells. In patients with EGFR mutations (most commonly exon 19 deletions or L858R point mutations), EGFR tyrosine kinase inhibitors (TKIs) are effective. These include:
- Erlotinib, Gefitinib, and Afatinib.
- These agents work by inhibiting the activity of EGFR, thereby blocking downstream signaling that promotes cancer cell growth.
(2) Anaplastic Lymphoma Kinase (ALK) Inhibitors:
- In ALK-positive NSCLC, typically found in younger, non-smokers, ALK inhibitors such as Crizotinib, Ceritinib, and Alectinib are used.
- These drugs target the ALK gene rearrangements, preventing the fusion protein from promoting tumor growth.
(3) Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) Inhibitors:
- Immune checkpoint inhibitors like Pembrolizumab and Nivolumab target the PD-1/PD-L1 pathway, which cancer cells use to evade the immune system. These agents work by reactivating T-cells to attack cancer cells.
- Pembrolizumab is used in cases where PD-L1 expression is high, and it has shown significant benefit in advanced-stage NSCLC.
(4) Vascular Endothelial Growth Factor (VEGF) Inhibitors:
- Bevacizumab is a monoclonal antibody that inhibits VEGF, preventing the formation of new blood vessels (angiogenesis) that tumors need to grow. It is used in combination with chemotherapy for certain NSCLC cases.
(5) BRAF Inhibitors:
- In BRAF V600E-mutant NSCLC, BRAF inhibitors like Dabrafenib and Trametinib are used. These agents target the mutated BRAF gene, which is involved in cancer cell growth.
Step 3: Benefits and Challenges of Molecular Targeted Therapy in NSCLC.
- Benefits: - Targeted therapies tend to be more effective with fewer side effects compared to traditional chemotherapy.
- These therapies can offer significant survival benefits and improve quality of life for patients with advanced or metastatic disease.
- Challenges: - Development of resistance to these therapies over time, often due to secondary mutations.
- These therapies are often expensive and may require genetic testing to identify the specific mutations.