OVERVIEW

INTRODUCTION

Kidney cancer, also known as renal cell carcinoma (RCC), is a common malignancy of the urinary system. It is most often detected incidentally during imaging for other health concerns. Common symptoms include hematuria (blood in urine), flank pain, and unexplained weight loss. Early-stage kidney cancer is often treatable with surgery, while advanced cases may require a combination of chemotherapy, immunotherapy, and integrative oncology therapies.

TRADITIONAL THERAPIES FOR KIDNEY CANCER

CHEMOTHERAPY

Chemotherapy is generally less effective for kidney cancer compared to other cancers; however, specific agents like gemcitabine and fluorouracil (5-FU) are sometimes used in combination with other treatments. Chemotherapy may be considered for certain aggressive forms of kidney cancer.

GEMCITABINE

Mechanism: Inhibits DNA synthesis by acting as a nucleoside analog, leading to apoptosis of cancer cells.

Clinical Applications: Sometimes used in advanced kidney cancer in combination with targeted agents.

Study Reference: Mack PC, Redman MW, Chansky K, et al. ‘Gemcitabine and doxorubicin in renal cancer.’ *Journal of Clinical Oncology*, 2004, 22(14):2845–2850.

FLUOROURACIL (5-FU)

Mechanism: Inhibits thymidylate synthase, disrupting DNA synthesis and inducing cancer cell death.

Clinical Applications: Occasionally used in combination therapy for advanced renal cell carcinoma (RCC).

Study Reference: Bukowski RM, Stadler WM, McDermott DF, et al. ‘Phase II trial of fluorouracil in patients with metastatic renal cell carcinoma.’ *Journal of Clinical Oncology*, 2005, 23(8):1583–1589.

IMMUNOTHERAPY AND CHECKPOINT INHIBITORS

NIVOLUMAB (OPDIVO)

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

Clinical Applications: Effective in advanced renal cell carcinoma, particularly after progression on other treatments.

Study Reference: Motzer RJ, Escudier B, McDermott DF, et al. ‘Nivolumab versus everolimus in advanced renal-cell carcinoma.’ *New England Journal of Medicine*, 2015, 373(19):1803–1813.

PEMBROLIZUMAB (KEYTRUDA)

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

Clinical Applications: Used in combination with axitinib for advanced renal cell carcinoma (RCC).

Study Reference: Rini BI, Plimack ER, Stus V, et al. ‘Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.’ *New England Journal of Medicine*, 2019, 380(12):1116–1127.

RADIATION THERAPY

Radiation therapy is typically used for palliative care in kidney cancer to reduce pain and control symptoms in metastatic sites. It is not commonly used as primary treatment due to radioresistance of renal cell carcinoma.

EXTERNAL BEAM RADIATION THERAPY (EBRT)

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

Clinical Applications: Mainly used to manage metastasis in bones and brain from kidney cancer.

Study Reference: Bianchi M, Sun M, Jeldres C, et al. ‘Distribution of metastatic sites in renal cell carcinoma: a population-based analysis.’ *Annals of Oncology*, 2012, 23(4):973–980.

TARGETED THERAPY

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

VEGF INHIBITORS (BEVACIZUMAB, AXITINIB, PAZOPANIB)

Mechanism: Inhibits vascular endothelial growth factor (VEGF), reducing tumor angiogenesis.

Clinical Applications: Commonly used in metastatic renal cell carcinoma (RCC) to prevent blood vessel growth in tumors.

Study Reference: Motzer RJ, Hutson TE, Cella D, et al. ‘Pazopanib versus sunitinib in metastatic renal-cell carcinoma.’ *New England Journal of Medicine*, 2013, 369(8):722–731.

MTOR INHIBITORS (EVEROLIMUS, TEMSIROLIMUS)

Mechanism: Blocks the mammalian target of rapamycin (mTOR) pathway, which is essential for cell growth and angiogenesis.

Clinical Applications: Effective in advanced RCC, particularly for poor-prognosis patients.

Study Reference: Hudes G, Carducci M, Tomczak P, et al. ‘Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.’ *New England Journal of Medicine*, 2007, 356(22):2271–2281.

INTEGRATIVE ONCOLOGY THERAPIES FOR KIDNEY 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 kidney cancer: Evidence from literature.’ *Kidney 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 kidney cancer cells.

Clinical Applications: Effective against metastatic renal cell carcinoma 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 renal cancer and resistant forms.

Study Reference: González P, Terrón MP, Martín-Rodríguez A, et al. ‘Ivermectin suppresses renal 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 renal cell carcinoma, particularly in diabetic patients.

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

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