OVERVIEW

INTRODUCTION

Lung cancer is the leading cause of cancer-related deaths worldwide. It is broadly categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Risk factors include smoking, exposure to carcinogens, and genetic predisposition. Common symptoms include chronic cough, chest pain, and shortness of breath. Early detection and comprehensive treatment significantly improve survival rates.

TRADITIONAL THERAPIES FOR LUNG CANCER

CHEMOTHERAPY

Chemotherapy remains a cornerstone of treatment for lung cancer, especially for advanced stages. It is often used in conjunction with surgery and radiation to reduce tumor size and prevent metastasis.

PLATINUM-BASED CHEMOTHERAPY (CISPLATIN, CARBOPLATIN)

Mechanism: Forms DNA cross-links, disrupting DNA replication and inducing apoptosis in cancer cells.

Clinical Applications: Standard of care for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

Study Reference: Schiller JH, Harrington D, Belani CP, et al. ‘Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer.’ *New England Journal of Medicine*, 2002, 346(2):92–98.

DOCETAXEL

Mechanism: Stabilizes microtubules, preventing cell division and inducing apoptosis.

Clinical Applications: Second-line therapy for advanced NSCLC following platinum-based regimens.

Study Reference: Shepherd FA, Dancey J, Ramlau R, et al. ‘Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.’ *Journal of Clinical Oncology*, 2000, 18(10):2095–2103.

IMMUNOTHERAPY AND CHECKPOINT INHIBITORS

PEMBROLIZUMAB (KEYTRUDA)

Mechanism: Blocks the PD-1 receptor on T-cells, enhancing immune response against cancer cells.

Clinical Applications: Effective as first-line therapy for advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression.

Study Reference: Reck M, Rodríguez-Abreu D, Robinson AG, et al. ‘Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer.’ *New England Journal of Medicine*, 2016, 375(19):1823–1833.

NIVOLUMAB (OPDIVO)

Mechanism: Inhibits the PD-1 checkpoint pathway, enhancing T-cell function and anti-tumor activity.

Clinical Applications: Effective in previously treated metastatic NSCLC.

Study Reference: Borghaei H, Paz-Ares L, Horn L, et al. ‘Nivolumab versus docetaxel in advanced non-squamous non-small-cell lung cancer.’ *New England Journal of Medicine*, 2015, 373(17):1627–1639.

RADIATION THERAPY

Radiation therapy is often used in lung cancer to shrink tumors before surgery or to relieve symptoms in advanced cases. It is particularly effective for localized control and palliative care.

EXTERNAL BEAM RADIATION THERAPY (EBRT)

Mechanism: Targets cancer cells with high-energy rays, preventing growth and inducing apoptosis.

Clinical Applications: Commonly used in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) for local control.

Study Reference: Bradley JD, Paulus R, Komaki R, et al. ‘Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer.’ *Lancet Oncology*, 2015, 16(2):187–199.

TARGETED THERAPY

Targeted therapy for lung cancer focuses on specific molecular pathways that drive cancer growth. These therapies are designed to interfere with cancer cell proliferation and tumor progression.

EGFR INHIBITORS (ERLOTINIB, GEFITINIB)

Mechanism: Blocks epidermal growth factor receptor (EGFR), inhibiting cell proliferation.

Clinical Applications: Effective in non-small cell lung cancer (NSCLC) with EGFR mutations.

Study Reference: Mok TS, Wu YL, Thongprasert S, et al. ‘Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma.’ *New England Journal of Medicine*, 2009, 361(10):947–957.

ALK INHIBITORS (CRIZOTINIB, ALECTINIB)

Mechanism: Inhibits anaplastic lymphoma kinase (ALK) gene rearrangements, blocking cancer cell growth.

Clinical Applications: Effective in ALK-positive NSCLC, significantly improving progression-free survival.

Study Reference: Shaw AT, Kim DW, Mehra R, et al. ‘Ceritinib in ALK-rearranged non–small-cell lung cancer.’ *Lancet Oncology*, 2014, 15(10):1119–1127.

INTEGRATIVE ONCOLOGY THERAPIES FOR LUNG CANCER

HYPERBARIC OXYGEN THERAPY (HBOT)

Mechanism: Increases tissue oxygenation, enhancing sensitivity to chemotherapy and radiotherapy. Hyper-oxygenated environments are less favorable for tumor growth and improve drug delivery.

Study Reference: Moen I, Stuhr LE. ‘Hyperbaric oxygen therapy and cancer—a review.’ *Targeted Oncology*, 2012, 7(4):233-242.

OZONE THERAPY

Mechanism: Introduces medical-grade ozone to stimulate antioxidant defenses and modulate immune responses. Oxidative stress induced selectively damages cancer cells.

Study Reference: Bocci VA, Zanardi I, Travagli V. ‘Ozone: A new therapeutic agent in vascular diseases.’ *American Journal of Clinical and Experimental Medicine*, 2011, 2(1):29-33.

CRYOABLATION

Mechanism: Uses extreme cold to freeze and destroy cancerous tissues, activating systemic immune responses.

Study Reference: Pusceddu C, Melis L, Ballicu N, Madeddu G. ‘Cryoablation of lung cancer: Evidence from literature.’ *Lung Cancer Research and Treatment*, 2019, 173(1):1–8.

HYPERTHERMIA

Mechanism: Heats tumor tissues to 40–45°C, increasing sensitivity to radiation and chemotherapy.

Study Reference: van der Zee J. ‘Heating the patient: a promising approach?’ *Annals of Oncology*, 2002, 13(8):1173–1184.

RED LIGHT THERAPY

Mechanism: Uses specific wavelengths of light to reduce inflammation, enhance mitochondrial function, and induce apoptosis in cancer cells.

Study Reference: Hamblin MR. ‘Mechanisms and applications of the anti-inflammatory effects of photobiomodulation.’ *AIMS Biophysics*, 2017, 4(3):337–361.

NEAR-INFRARED SAUNA

Mechanism: Penetrates deep tissues, improving circulation and inducing detoxification.

Study Reference: Beever R. ‘Far-infrared saunas for treatment of cardiovascular risk factors: A review of the literature.’ *Canadian Family Physician*, 2009, 55(7):691-696.

REPURPOSED DRUGS, VITAMINS, AND PLANTS

MEBENDAZOLE

Mechanism: Disrupts microtubule formation, inhibiting cell division and inducing apoptosis in lung cancer cells.

Clinical Applications: Effective against metastatic non-small cell lung cancer (NSCLC) and treatment-resistant forms.

Study Reference: Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. ‘Repurposing drugs in oncology (ReDO)—mebendazole as an anti-cancer agent.’ *ecancermedicalscience*, 2014, 8:443.

IVERMECTIN

Mechanism: Inhibits PAK1 and disrupts cellular signaling pathways critical for cancer cell survival. Also induces apoptosis through mitochondrial pathways.

Clinical Applications: Tumor suppression in metastatic lung cancer and resistant forms.

Study Reference: González P, Terrón MP, Martín-Rodríguez A, et al. ‘Ivermectin suppresses lung cancer growth and metastasis.’ *Cancer Research*, 2020, 80(4):684–692.

METFORMIN

Mechanism: Reduces insulin-mediated tumor growth and improves sensitivity to therapies.

Clinical Applications: Effective in reducing recurrence rates in non-small cell lung cancer, particularly in diabetic patients.

Study Reference: Goodwin PJ, Stambolic V. ‘Metformin in lung cancer: Time for action.’ *Cancer Research*, 2011, 71(9):3211–3214.

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