Cancer Pathophysiology

Carcinogenesis and Pathophysiology

• Carcinogenesis is the development of cancer
• Oncogenes are altered genes that promote tumor growth and change programmed cell death (apoptosis)
• Tumor suppressor genes are the opposite of oncogenes; these genes become deactivated in cancer cells
• Approximately 5%-10% of all cancers have been shown to occur as a result of inherited genetic alterations

Phases of Cancer

• A carcinogen is a physical, chemical, or viral agent that induces cancer
• Carcinogenesis is a biologic, multistage process that proceeds on a continuum in three distinct phases: initiation, promotion, and progression
• Initiation involves transformation of cells produced by the interaction of chemicals, radiation, or viruses with DNA
• Transformation occurs rapidly, but cells can remain dormant for a variable period until they are activated by a promoting agent
• During promotion, initiated cells multiply and escape the mechanisms set in place to protect the body from the growth and spread of such cells
• A neoplasm, new and abnormal tissue with no useful function, is established
• In the third phase (progression), tumor cells aggregate and grow into a fully malignant neoplasm or a tumor
• In the process known as metastasis, the neoplasm has the capacity for tissue invasion that can spread to distant tissues and organs

Etiology

• Nutrition may modify the carcinogenic process at any stage, including carcinogen metabolism, cellular and host defense, cell differentiation, and tumor growth
• Gene expression can be promoted or altered by nutrients during pregnancy, childhood, and throughout a lifetime
• Thus, nutrition and diet contribute approximately 35% to causal factors for cancer
• Food preparation and preservation methods may also provide dietary carcinogens
• Diets contain both inhibitors and enhancers of carcinogenesis
• Inhibitors: antioxidants (vit C, vit E, selenium, carotenoids), phytochemicals (anthocyanins, lycopene, indoles, sulforaphanes)
• Enhancers: fat in red meat, polycyclic aromatic hydrocarbons that form with grilling meat, alcohol

Treatment and Response

• Goals of treatment: cure, control, palliate
• Factors that affect response: tumor burden, rate of tumor growth, drug resistance, comorbid diseases
• Response to treatment: complete or partial response (improvement), stable disease (stable), disease progression (worsening)

Nutrition and Cancer

• Nutrition-focused physical examination is recommended to evaluate fully nutrition status and degree of risk
• Energy needs increase in the presence of fever, stress, infection, metabolic complication, and tumor burden
• Protein needs increase because of metabolic stress and illness, with requirements of 1.2g/kg/day or more
• Vitamins, minerals, and supplementation: controversial studies, standard multivitamin and mineral supplement recommended
• Nutrition intervention strategies: oral nutrition management, food and presentation modification, liquid medical food supplements, managing anorexia and alterations in taste and smell

Cancer Cachexia

• Tumor increases demand for glucose, leading to anaerobic glycolysis and lactate production
• Protein breakdown and lipolysis increase to compensate for glucose need and energy needs
• Glucose intolerance and insulin resistance occur
• Loss of protein: amino acids are taken by the tumor to increase in size
• Cancer cachexia is characterized by progressive weight loss, anorexia, wasting, weakness, immunosuppression, and abnormal fluid and energy metabolism