What is Cancer
Cancer is a disease characterized by uncontrolled proliferation of transformed cells that have evaded normal growth control mechanisms and are subject to evolution by natural selection, with the potential to invade surrounding tissues and spread to distant sites in the body. 1
Fundamental Biological Definition
At the molecular level, cancer represents a multihit disease resulting from accumulation of genetic mutations and alterations in genes controlling cell growth, programmed death, differentiation, and cell-tissue architecture. 2 These mutations are inheritable at the somatic level, meaning they pass through cancer cell generations. 2
Cancer should be understood as a disease of signaling networks within cells rather than simply a collection of individual mutations. 2 Different cancers tend to be more similar in terms of altered signaling pathways than in the specific individual mutations present in any given pathway, and mutations within a pathway can be partially interchangeable and mutually exclusive. 2
Cellular Transformation and Progression
The disease begins as a clonal proliferation of cells that have acquired distinct mutations, which then progress to invasive carcinoma as cells breach the underlying basement membrane associated with the tissue of origin. 3 This transition to invasive carcinoma carries the potential to invade blood vessels or lymphatic channels and metastasize to lymph nodes or distant tissues, resulting in increased morbidity and mortality. 3
Carcinoma specifically refers to cancer arising from epithelial cells that line organs or tissues. 3 The histologic diagnosis is rendered based on both cytologic and architectural features of the tumor, the location of proliferating cells, and their interaction with surrounding stromal elements. 3
Tumor Heterogeneity and Evolution
Significant tumor heterogeneity exists both between patients and even within the same tumor. 2 Cancer cells are subject to evolution by natural selection, with genetic and epigenetic changes accumulating within the cancer cell population that lead to increasingly lethal phenotypes. 1 This includes somatically inheritable epigenetic alterations, particularly methylation of promoter region CpG islands. 2
Clinical Impact and Burden
Cancer is the second leading cause of death in the United States and worldwide, responsible for 1.6 million deaths domestically and 8.8 million deaths globally annually. 2 Approximately 20 million new cases were diagnosed worldwide in 2020. 2 The disease accounts for nearly one in six deaths globally. 2
Approximately 20% of all cancers diagnosed in the United States are attributable to unhealthy diet, excessive alcohol consumption, physical inactivity, and body fatness. 2 The global economic impact exceeds $1.16 trillion annually and is expected to increase by 70% within two decades. 2
Immune System Interactions
Cancer cells evolve strategies that target many aspects of the immune system to escape or edit immune surveillance. 4 The immunosuppressive tumor microenvironment represents a major obstacle in cancer therapy development. 4 The dynamic interactions between the immune system and cancer development have led to the emergence of nutritional immunology as a field. 4