Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy.

Metastatic cancers are associated with cellular oxidative stress, and during cancer chemotherapy excess drug-induced oxidative stress can limit therapeutic effectiveness and cause a number of side effects, including fatigue, nausea, vomiting, diarrhea and more serious adverse effects, such as cardiomyopathy, peripheral neuropathy, hepatotoxicity and pulmonary fibrosis. We review here the hypothesis that the acute and chronic adverse effects of cancer chemotherapy can be reduced by molecular replacement of membrane lipids and enzymatic cofactors, such as coenzyme Q(10). By administering nutritional supplements with replacement molecules and antioxidants, oxidative membrane damage and reductions of cofactors in normal tissues can be reversed, protecting and restoring mitochondrial and other cellular functions and reducing chemotherapy adverse effects.

Molecular Replacement for Cancer Metabolic and Mitochondrial Dysfunction, Fatigue and the Adverse Effects of Cancer Therapy.

During cancer treatment drug-induced oxidative stress can limit the effectiveness of therapy and cause a number of side effects such as fatigue, nausea, vomiting and diarrhea, as well as more serious adverse effects including cardiomyopathy, peripheral neuropathy, hepatotoxicity and pulmonary fibrosis. Many of these adverse effects are due to oxidative stress-mediated damage to normal tissues. Antioxidant administration and molecular replacement can mitigate the damage to normal tissues and reduce the adverse effects of cancer therapy without loss of therapeutic potential.

Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity.

Preclinical and clinical studies suggest that anthracycline-induced cardiotoxicity can be prevented by administering coenzyme Q10 during cancer chemotherapy that includes drugs such as doxorubicin and daunorubicin. Studies further suggest that coenzyme Q10 does not interfere with the antineoplastic action of anthracyclines and might even enhance their anticancer effects. Preventing cardiotoxicity might allow for escalation of the anthracycline dose, which would further enhance the anticancer effects.

Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness.

Antineoplastic agents induce oxidative stress in biological systems. During cancer chemotherapy, oxidative stress-induced lipid peroxidation generates numerous electrophilic aldehydes that can attack many cellular targets. These products of oxidative stress can slow cell cycle progression of cancer cells and cause cell cycle checkpoint arrest, effects that may interfere with the ability of anticancer drugs to kill cancer cells.

Dietary polyunsaturated fatty acids: impact on cancer chemotherapy and radiation.

Preclinical studies have shown that certain polyunsaturated fatty acids may actually enhance the cytotoxicity of several antineoplastic agents and the anticancer effects of radiotherapy. These effects are possibly mediated by incorporation of the polyunsaturated fatty acids into cancer cell membranes, thus altering the physical and functional properties. In addition, certain polyunsaturated fatty acids may also reduce or prevent some of the side effects of these therapies, and administering antioxidants to prevent polyunsaturated fatty acid-induced oxidative stress may further enhance the impact of chemotherapy and radiation.