2.

- Cáncer
 Las preguntas claves:

• Diferencia entre mutación y cáncer

• Carcinogénesis: una o multi-etapas ?
• Mutación somática vs cambio epigenético
• Enfermedad genética o hereditaria ?
• Rol de factores externos
 Crecimiento autónomo de un tejido (Ewing, 1940)

Lesión al Reparación Célula iniciada

del ADN (mutación)
Cáncer
ADN
 Epidemiología y datos….

…Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast
(1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000
deaths), and stomach cancer (723,000 deaths)….. Ferlay et al, Int, J Cancer 2015 136: E359-386
Como evoluciona un cáncer ?
Las características distintivas de las células cancerosas
Metástasis y angiogénesis
La causa de un cáncer sería la modificación
de un solo gen responsable del control del
crecimiento celular (mutación somática).

El cáncer sería un caso particular de la

ecuación  Evolución = mutación x azar
selección

Pero no todo es ADN, también existen

los mecanismos epigenéticos.
Solo una pequeña parte del ADN es leída !!
 Es el cáncer una
enfermedad hereditaria ?
(2-3/dia)
Cigarette smoke has both pro-inflammatory and immunosuppressive effects on the immune system. Acute effects of smoke on macrophages and epithelial
cells promote inflammation by inducing the recruitment of cells from the microcirculation to the lungs. At the same time, cigarette smoke impairs innate defence
mechanisms that are mediated by macrophages, epithelial cells, dendritic cells (DCs) and natural killer (NK) cells, thereby increasing the risk, severity and
duration of infection. The transition to a more severe expression of smoking-associated disease is marked by the impaired ability of macrophages to kill bacteria
or viruses, the loss of the ability to remove dead cells, the degradation and chemical modification of the extracellular matrix, the increasing retention of
oligoclonally expanded CD8+ T cells and the induction of interleukin-17 (IL-17)-secreting effector T cells. After long-term exposure to cigarette smoke, lymphoid
aggregates with T cells and B cell zones may form at the site, supporting the production of pathogenic autoantibodies and driving autoimmune disease. Loss of
mucosal defences can lead to bacterial colonization (as occurs in around 30% of long-term smokers with chronic obstructive pulmonary disease (COPD)).
Concurrently somatic mutations in the epithelium and alteration of macrophage phenotype promote inflammation and the development of cancer (carcinoma in
situ) that has a high chance of metastatic spread. CTL, cytotoxic T lymphocyte; TAM, tumour-associated macrophage; TH17, T helper 17; TReg, regulatory T.
 Estimación del número de muertes (los 10 tipos de cáncer
mas frecuentes), ambos sexos, en todo el mundo en 2012

Pulmón
Hígado
Estomago
Colorectal
Mamario
Esófago
Páncreas
Próstata
Cervical
Leucemia

Data source: GLOBOCAN 2012

Graph production: Cancer Today (http://gco.iarc.fr/today)
© International Agency for Research on Cancer 2016