We present an integrative understanding of cancer as a metabolic multifactorial, multistage disease. We focus on underlying genetics-environmental interactions, evidenced by telomere changes. A range of genetic and epigenetic factors, including physical agents and predisposing factors such as diet and lifestyle are included. We present a structured model of the causes of cancer, methods of investigations, approaches to cancer prevention, and polypharmaceutical multidisciplinary complex treatment within a framework of personalized medicine. We searched PubMed, National Cancer Institute online, and other databases for publications regarding causes of cancer, reports of novel mitochondrial reprogramming, epigenetic, and telomerase therapies and state-of-the-art investigations. We focused on multistep treatment protocols to enhance early detection of cancer, and elimination or neutralization of the causes and factors associated with cancer formation and progression. Our aim is to suggest a model therapeutic protocol that incorporates the patient's genome, metabolism, and immune system status; stage of tumor development; and comorbidity(ies), if any. Investigation and treatment of cancer is a challenge that requires further holistic studies that improve the quality of life and survival rates, but are most likely to aid prevention.
Keywords: DNA damage; cancer; epigenetic; genotoxic; lifestyle; metabolism; senescence; stress; telomeres; therapies.