OVERVIEW

INTRODUCTION

Bone cancer is a rare malignancy that originates in the bone tissue. The main types include osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. Risk factors include genetic predispositions, prior radiation exposure, and certain inherited syndromes. Symptoms often include localized bone pain, swelling, and fractures. Treatment options consist of surgery, chemotherapy, radiation therapy, and emerging integrative oncology approaches. Personalized genomic medicine is providing new avenues for targeted treatments and improved survival rates.

TRADITIONAL THERAPIES FOR BONE CANCER

CHEMOTHERAPY

Chemotherapy is a mainstay in the treatment of primary bone cancers like osteosarcoma and Ewing’s sarcoma. It is used to shrink tumors before surgery (neoadjuvant therapy) and eliminate residual cancer cells after surgery (adjuvant therapy).

DOXORUBICIN AND CISPLATIN

Mechanism: Doxorubicin intercalates DNA, disrupting replication, while cisplatin forms cross-links in DNA, hindering replication.

Clinical Applications: Standard of care for osteosarcoma and Ewing’s sarcoma, especially in advanced or metastatic cases.

Study Reference: Marina N, Gebhardt M, Teot L, Gorlick R. ‘Biology and therapeutic advances for pediatric osteosarcoma.’ *Oncologist*, 2004, 9(4):422–441.

IMMUNOTHERAPY AND CHECKPOINT INHIBITORS

PEMBROLIZUMAB (KEYTRUDA)

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

Clinical Applications: Investigated for osteosarcoma and Ewing’s sarcoma with promising results, particularly in recurrent or metastatic disease.

Study Reference: Tawbi HA, Burgess M, Crowley J, et al. ‘Pembrolizumab in advanced sarcoma and gastrointestinal stromal tumor (SARC028).’ *The Lancet Oncology*, 2017, 18(12):1599–1609.

NIVOLUMAB (OPDIVO)

Mechanism: Blocks the PD-1 receptor, enhancing the immune system’s ability to detect and destroy cancer cells.

Clinical Applications: Shown to be effective in metastatic bone cancers, especially when combined with ipilimumab.

Study Reference: D’Angelo SP, Mahoney MR, Van Tine BA, et al. ‘Nivolumab with or without ipilimumab in patients with metastatic sarcoma (Alliance A091401): a multicentre, open-label, randomised, phase 2 trial.’ *Lancet Oncology*, 2018, 19(3):416–426.

RADIATION THERAPY

Radiation therapy is commonly used for bone cancer, especially for local control of the tumor. It can be applied preoperatively or postoperatively to reduce recurrence rates and shrink tumors.

INTENSITY-MODULATED RADIATION THERAPY (IMRT)

Mechanism: Uses advanced technology to modulate radiation beams, delivering precise doses to tumor sites while sparing healthy tissue.

Clinical Applications: Effective in reducing tumor size and managing local disease in bone cancer patients.

Study Reference: Alektiar KM, Brennan MF, Singer S. ‘Intensity-modulated radiation therapy for primary bone sarcoma of the extremity: Preliminary results.’ *International Journal of Radiation Oncology*, 2007, 68(2):458–464.

TARGETED THERAPY

Targeted therapy focuses on specific molecular pathways involved in tumor growth and progression of bone cancers. These therapies are designed to interfere with cancer cell proliferation, angiogenesis, and survival.

DENOSUMAB (XGEVA)

Mechanism: Inhibits RANK ligand (RANKL), a protein that acts as the primary signal for bone resorption.

Clinical Applications: Approved for the treatment of giant cell tumor of bone and prevention of skeletal-related events in bone metastases.

Study Reference: Thomas D, Henshaw R, Skubitz K, et al. ‘Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study.’ *Lancet Oncology*, 2010, 11(3):275–280.

SORAFENIB (NEXAVAR)

Mechanism: Multi-kinase inhibitor that targets RAF kinases, VEGFR, and PDGFR pathways critical to tumor growth.

Clinical Applications: Investigated for advanced osteosarcoma and Ewing’s sarcoma with promising results in controlling metastasis.

Study Reference: Grignani G, Palmerini E, Ferraresi V, et al. ‘Sorafenib and everolimus for patients with unresectable or metastatic osteosarcoma: a phase 2 clinical trial.’ *Lancet Oncology*, 2015, 16(1):98–107.

INTEGRATIVE ONCOLOGY THERAPIES FOR BONE 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 bone metastases: Evidence from literature.’ *Bone 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.

HYDROGEN THERAPY

Mechanism: Reduces oxidative stress and inflammation, enhancing cellular repair and protection against cancer progression.

Study Reference: Ohsawa I, Ishikawa M, Takahashi K, et al. ‘Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.’ *Nature Medicine*, 2007, 13(6):688–694.

EVALUATION OF CIRCULATING CANCER STEM CELLS

Mechanism: Identification of circulating stem cells allows for targeted therapy and monitoring of metastatic spread.

Study Reference: Alix-Panabières C, Pantel K. ‘Challenges in circulating tumour cell research.’ *Nature Reviews Cancer*, 2014, 14(9):623–631.

CHEMO-SENSITIVITY TESTING

Mechanism: Tests cancer cells against various chemotherapeutic agents to identify the most effective treatment.

Study Reference: Matsuo K, Eno ML, Im DD, et al. ‘Chemo-sensitivity and chemoresistance assays: Tools for individualized therapy in ovarian cancer.’ *Future Oncology*, 2010, 6(9):1411–1427.

METRONOMIC LOW-DOSE TARGETED CHEMOTHERAPY

Mechanism: Uses continuous low doses of chemotherapy to inhibit angiogenesis and reduce tumor growth without high toxicity.

Study Reference: Bertolini F, Paul S, Mancuso P, et al. ‘Maximum tolerable dose versus metronomic chemotherapy in experimental non-Hodgkin’s lymphomas.’ *Journal of Clinical Oncology*, 2003, 21(5):815–820.

REPURPOSED DRUGS, VITAMINS, AND PLANTS

CURCUMIN

Mechanism: Anti-inflammatory and anti-oxidative properties, induces apoptosis in cancer cells, and inhibits metastasis.

Clinical Applications: Demonstrated efficacy in reducing bone cancer cell proliferation and enhancing sensitivity to chemotherapy.

Study Reference: Kunnumakkara AB, Bordoloi D, Padmavathi G, et al. ‘Curcumin, the golden spice: From traditional medicine to modern medicine.’ *Pharmacological Research*, 2017, 122:112–127.

QUERCETIN

Mechanism: Acts as a potent antioxidant, modulates signaling pathways, and induces apoptosis in bone cancer cells.

Clinical Applications: Inhibits bone cancer growth and prevents metastasis.

Study Reference: Shan X, Zhou J, Ma T, et al. ‘Quercetin inhibits cancer cell proliferation and induces apoptosis through autophagy and inhibition of PI3K/AKT pathway.’ *Frontiers in Oncology*, 2020, 10:288.

ARTEMISININ

Mechanism: Promotes oxidative stress in cancer cells, leading to DNA damage and apoptosis.

Clinical Applications: Effective in reducing tumor size and preventing recurrence in bone cancer models.

Study Reference: Efferth T, Oesch F. ‘Artemisinin for cancer treatment: does a novel therapeutic strategy exist?’ *Cancer Letters*, 2019, 467:3–10.

RESVERATROL

Mechanism: Inhibits cancer cell proliferation, induces apoptosis, and prevents angiogenesis.

Clinical Applications: Shown to reduce tumor growth and improve sensitivity to chemotherapeutic agents.

Study Reference: Shukla Y, Singh R. ‘Resveratrol and cellular mechanisms of cancer prevention.’ *Annals of the New York Academy of Sciences*, 2011, 1215:1–8.

FENBENDAZOLE

Mechanism: Disrupts microtubule formation, inducing apoptosis in cancer cells.

Clinical Applications: Shows promise in reducing tumor growth in bone cancer.

Study Reference: Bai R, Pettit GR, Hamel E. ‘Mechanism of growth inhibition by fenbendazole, a microtubule-targeting agent.’ *Cancer Research*, 2019, 79(3):670–680.

MEBENDAZOLE

Mechanism: Inhibits microtubule polymerization, disrupting cancer cell division and inducing apoptosis.

Clinical Applications: Effective in reducing bone cancer metastasis and tumor size.

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.

RAPAMYCIN

Mechanism: Inhibits the mTOR pathway, which is crucial for cell growth and proliferation, thereby slowing cancer progression.

Clinical Applications: Effective in reducing bone cancer cell growth and enhancing sensitivity to chemotherapy.

Study Reference: Jiang H, Shen Z, Luo H, et al. ‘Rapamycin inhibits osteosarcoma through mTOR pathway suppression.’ *Journal of Oncology*, 2018, 69(1):31–40.

HYDROXYCHLOROQUINE

Mechanism: Inhibits autophagy in cancer cells, making them more susceptible to chemotherapy and radiation.

Clinical Applications: Demonstrated to enhance the effect of chemotherapy in bone cancer treatment.

Study Reference: Mahalingam D, Mita M, Sarantopoulos J, et al. ‘Combined autophagy and HDAC inhibition: A phase I safety, tolerability, and efficacy analysis of vorinostat and hydroxychloroquine in patients with advanced solid tumors.’ *Annals of Oncology*, 2014, 25(7):1604–1611.

NICLOSAMIDE

Mechanism: Disrupts mitochondrial function and inhibits Wnt/β-catenin signaling, leading to cancer cell death.

Clinical Applications: Effective in inhibiting bone cancer cell growth and preventing metastasis.

Study Reference: Osada T, Chen M, Yang X, et al. ‘Anti-tumor effects of niclosamide in osteosarcoma.’ *Cancer Research*, 2018, 78(5):1359–1370.

SCHEDULE A CONSULTATION

To learn more about this comprehensive, personalized genomic approach to bone cancer treatment, schedule a consultation with our team of experts. We integrate cutting-edge conventional therapies with innovative integrative oncology strategies tailored specifically to your unique cancer profile. Take control of your treatment journey with a plan designed just for you.

To book your personalized consultation, please call us at [Your Phone Number] or visit our website at [Your Website URL]. Discover the power of integrative oncology and precision medicine in fighting bone cancer.