Anticancer Drugs for Lung Cancer

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Anticancer Drugs for Lung Cancer

Lung cancer treatment depends on the type of lung cancer, its genetic mutations, and the stage at diagnosis. The main categories of anticancer drugs used for lung cancer include chemotherapy, targeted therapy, immunotherapy, and antibody-drug conjugates (ADCs). Below is an overview of the key drugs in each category.

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1. Chemotherapy

Chemotherapy remains a cornerstone in lung cancer treatment, particularly for small-cell lung cancer (SCLC) and advanced non-small cell lung cancer (NSCLC) without targetable mutations.

Platinum-Based Chemotherapy (Backbone for Many Regimens)

• Cisplatin: Alkylating agent that binds to DNA, causing cross-linking and apoptosis.
• Carboplatin: Similar to cisplatin but with fewer nephrotoxic effects, often used in patients with poor renal function.

Other Common Chemotherapeutic Agents

• Pemetrexed (Alimta) – Used in non-squamous NSCLC, inhibits folate-dependent enzymes.
• Gemcitabine – Inhibits DNA synthesis, commonly used for squamous NSCLC.
• Docetaxel and Paclitaxel – Microtubule inhibitors that prevent cell division.
• Etoposide – Topoisomerase II inhibitor, frequently used for SCLC.
• Vinorelbine – A mitotic inhibitor, often combined with platinum agents.

Chemotherapy is usually combined with radiation therapy in localized disease or immunotherapy in advanced NSCLC.

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2. Targeted Therapy

Targeted therapy is used in NSCLC patients with specific genetic mutations, often detected via next-generation sequencing (NGS). These drugs are typically tyrosine kinase inhibitors (TKIs).

For EGFR Mutations (Exon 19 deletion, L858R, etc.)

• Osimertinib (Tagrisso) – Third-generation TKI, highly selective, effective against T790M resistance mutation.
• Erlotinib, Gefitinib, Afatinib – First- and second-generation TKIs.

For ALK Rearrangements

• Alectinib (Alecensa) – First-line ALK inhibitor, superior to crizotinib.
• Crizotinib, Brigatinib, Lorlatinib – Other ALK inhibitors with varying resistance profiles.

For ROS1 Rearrangements

• Crizotinib – Also effective against ROS1-positive NSCLC.
• Entrectinib – Approved for ROS1 and NTRK fusion-positive lung cancer.

For MET Exon 14 Skipping Mutations

• Capmatinib, Tepotinib – MET inhibitors used in NSCLC with MET exon 14 alterations.

For RET Fusion-Positive NSCLC

• Selpercatinib, Pralsetinib – RET inhibitors with high efficacy.

For BRAF V600E Mutation

• Dabrafenib + Trametinib – Combination of BRAF and MEK inhibitors.

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3. Immunotherapy

Immunotherapy has revolutionized lung cancer treatment by enhancing the immune system’s ability to recognize and kill cancer cells. It is mainly used in NSCLC with high PD-L1 expression (≥50%) or in combination with chemotherapy.

Immune Checkpoint Inhibitors (ICIs)

• Pembrolizumab (Keytruda) – Anti-PD-1 monoclonal antibody, first-line for NSCLC with PD-L1 ≥50%.
• Nivolumab (Opdivo) – Anti-PD-1, used in later-line settings.
• Atezolizumab (Tecentriq) – Anti-PD-L1 antibody, used for NSCLC and SCLC.
• Durvalumab (Imfinzi) – Anti-PD-L1, used as consolidation therapy after chemoradiotherapy in stage III NSCLC.

ICIs are often combined with chemotherapy (e.g., Pembrolizumab + Carboplatin/Pemetrexed) for improved survival.

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4. Antibody-Drug Conjugates (ADCs)

ADCs are emerging as a promising therapy in NSCLC by delivering cytotoxic drugs directly to cancer cells.

Approved ADCs

• Trastuzumab deruxtecan (Enhertu) – HER2-targeted ADC for NSCLC with HER2 mutations.
• Datopotamab deruxtecan (Dato-DXd) – A new ADC targeting TROP2 in NSCLC, under investigation.

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5. Experimental and Emerging Therapies

• KRAS G12C Inhibitors: Sotorasib (Lumakras), Adagrasib – Target KRAS mutations, a previously "undruggable" mutation.
• Bispecific Antibodies: Novel agents that target two pathways simultaneously.
• Tumor Vaccines & Cell Therapies: Research is ongoing for lung cancer vaccines and CAR-T therapies.

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Choosing the Right Treatment

• NSCLC with driver mutations → Targeted therapy.
• NSCLC without driver mutations, PD-L1 ≥50% → Immunotherapy.
• NSCLC without driver mutations, PD-L1 <50% → Chemotherapy + Immunotherapy.
• SCLC → Chemotherapy + Immunotherapy.

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Conclusion

Lung cancer treatment has evolved dramatically with the advent of targeted therapies and immunotherapy, significantly improving survival. The choice of therapy depends on molecular testing, histological subtype, and disease stage. Ongoing research continues to expand treatment options, particularly with ADCs and novel targeted agents.

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Next Questions

1. How do resistance mechanisms develop in targeted lung cancer therapy, and what are the strategies to overcome them?
2. What are the latest advancements in lung cancer immunotherapy, and how do they compare to traditional chemotherapy?
3. How does the effectiveness of first-line targeted therapies differ based on genetic mutations in NSCLC?

 

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