Hallmarks of cancer (Weinberg. cell, 2011) Sustaining Evading proliferative growth signaling suppressors Deregulating Avoiding cellular Immune energetics destruction Resistin Enable cell replicative death immortality G enome instability promoting mutation inflammation Inducing Activating angiogenesis invasion metastasis (Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation Cell 2011, 144: 646)6
6 Hallmarks of cancer (Weinberg, Cell, 2011) . (Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell 2011, 144:646)
The hallmarks of cancer Self-sufficiency in growth signals Cancer cells do not need stimulation from external signals ( in the form of growth factors) to multiply Insensitivity to anti-growth signals Cancer cells are generally resistant to growth-preventing signals from their neighbours Tissue invasion and metastasis Cancer cells can break away from their site or organ of origin to invade surrounding tissue and spread(metastasis)to distant body parts Limitless reproductive potential Non-cancer cells die after a certain number of divisions cancer cells escape this limit and are apparently capable of indefinite growth and division(immortality) Sustained angiogenesis Cancer cells appear to be able to kickstart this process, ensuring that such cells receive a continual supply of oxygen and other nutrients Evading apoptosis Apoptosis is a form of programmed cell death, the mechanism by which cells are programmed to die after a certain number of divisions or in the event they become damaged. Cancer cells characteristically are able to bypass this 7 mechanism
7 The Hallmarks of Cancer Self-sufficiency in growth signals Cancer cells do not need stimulation from external signals (in the form of growth factors) to multiply. Insensitivity to anti-growth signals Cancer cells are generally resistant to growth-preventing signals from their neighbours. Tissue invasion and metastasis Cancer cells can break away from their site or organ of origin to invade surrounding tissue and spread (metastasis) to distant body parts. Limitless reproductive potential Non-cancer cells die after a certain number of divisions. Cancer cells escape this limit and are apparently capable of indefinite growth and division (immortality). Sustained angiogenesis Cancer cells appear to be able to kickstart this process, ensuring that such cells receive a continual supply of oxygen and other nutrients. Evading apoptosis Apoptosis is a form of programmed cell death, the mechanism by which cells are programmed to die after a certain number of divisions or in the event they become damaged. Cancer cells characteristically are able to bypass this mechanism
Deregulated metabolism Most cancer cells use abnormal metabolic pathways to generate energy, a fact appreciated since the early twentieth century with the postulation of the Warburg hypothesis, but only now gaining renewed research interest Evading the immune system Cancer cells appear to be invisible to the body' s immune system Unstable dna Cancer cells generally have severe chromosomal abnormalities, which worsen as the disease progresses Inflammation Recent discoveries have highlighted the role of local chronic inflammation in inducing many types of cancer (Hanahan, D. Weinberg, R A(2011). Hallmarks of Cancer: The Next Generation". Cell 144(5):646-674.c0:10.1016cel201102.013)
8 Deregulated metabolism Most cancer cells use abnormal metabolic pathways to generate energy, a fact appreciated since the early twentieth century with the postulation of the Warburg hypothesis, but only now gaining renewed research interest. Evading the immune system Cancer cells appear to be invisible to the body’s immune system. Unstable DNA Cancer cells generally have severe chromosomal abnormalities, which worsen as the disease progresses. Inflammation Recent discoveries have highlighted the role of local chronic inflammation in inducing many types of cancer. (Hanahan, D.; Weinberg, R. A. (2011). "Hallmarks of Cancer: The Next Generation". Cell 144 (5): 646–674. doi:10.1016/j.cell.2011.02.013 )
Chemical Carcinogenesis Multi-stage Theory of Chemical Carcinogenesis Classification of chemical carcinogens Mechanisms of Chemical Carcinogenesis DNA Damage Induced by Ultimate Carcinogens ◆ DNA Repair
Chemical Carcinogenesis ◆ Multi-stage Theory of Chemical Carcinogenesis ◆ Classification of chemical carcinogens ◆ Mechanisms of Chemical Carcinogenesis ◆ DNA Damage Induced by Ultimate Carcinogens ◆ DNA Repair
Multi-stage Theory of Chemical Carcinogenesis Initiation --------Genetic events Chemical Carcinogens(Direct and Indirect Carcinogens) Promotion Epigenetic events Tumor promoters Murine skin carcinogenesis model A single dose of polycyclic aromatic hydrocarbon(PAH, Initiator) Repeated doses of croton oil(promoter) Malignant conversion Progression -----Genetic and epigenetic events
10 Multi-stage Theory of Chemical Carcinogenesis Initiation -----------Genetic events Chemical Carcinogens (Direct and Indirect Carcinogens) Promotion -------Epigenetic events Tumor promoters – Murine skin carcinogenesis model: • A single dose of polycyclic aromatic hydrocarbon (PAH, initiator) • Repeated doses of croton oil (promoter) Malignant conversion Progression ------Genetic and epigenetic events