TEMA - 05

Neoplasia
Part II

FISIOPATOLOGÍA
Prof. Javier Pereda
Prof. Julián Carretero
 Adult cancer
90% of the cases!
Most of them are
carcinomas
(epithelial origin)

Pediatric cancer

Vogelstein et al., Science 2013

 Cancer Genome Landscape
 Aging
Sporadic tumors have
 Inheretance
 Random DNA replication errors
hundreds/thousands of molecular
 Exposure to carcinogens alterations and their frequency is
Smoke highly heterogeneous.
Radiation (UV, X-rays…)
Infections, chronic inflammation
Contaminants
Dietary carcinogens…

Vogelstein et al., Science 2013

 Cancer incidence and mortality
 Incidence: how many people are diagnosed with cancer.
 Mortality: the number of deaths from cancer.
 Usually expressed as rates per 100,000 per year.
(2012)
Evolution of cancer mortality

Rates per 100,000; USA, males.

 Evolution of cancer survival
 Survival rate: % of survivors X years (1, 5, 10…) after cancer diagnosis.

Why?
 Early (and better) diagnostic tools
(MRI, CT, molecular tests).
 Better surgical procedures.
 Genetic and biological knowledge
leads to better (and targeted)
therapies.

 … but not for all cancer types…

Age-standardised 10-year net-survival trends for

adults aged 15-99, selected cancers, UK.
 Breast Cancer
 Most commmon cancer in women world-wide.

 As a result of improved treatment and earlier detection

(mammography screening), the mortality rate has begun to
decrease substantially.

 Heterogeneous group of diseases arising from breast tissue,

that differ in their prognosis and treatments. Most common:
ductal adenocarcinoma (epithelial).

 Hormonal cancer: it requires hormonal supply (estrogens) to

develop and grow. (→ many patients respond to hormonal
therapies!).

 Risk factors: age, hereditary factors (p.e., BRCA1 mutations),

endocrine & reproductive factors, carcinogen exposure (alcohol,
smoke, X- and γ-radiation).

 Signs and symptoms: breast mass, nipple discharge, mastalgia.

Breast Cancer
 Prostate Cancer
 Most commmon cancer in men world-wide.

 90% of men (>80 years old) show hyperplasia.

 Prostate cancer deaths has decreased (because early

detection, widespread use of PSA-based detection strategies,
hormonal therapies).

 Almost all are adenocarcinomas developed from epithelial

gland cells.

 Hormonal cancer: many of them require hormonal supply

(DHT) to develop and grow (→ they respond to hormonal
therapies!).

 Risk factors: age, hereditary factors (p.e., BRCA2 mutations),

diet factors (?).

 Signs and symptoms: urinary frequency, infection, urethral

obstruction...
 Lung Cancer
 Leading cause of cancer deaths world-wide,
incidence closely matches mortality: lack of early
diagnostic tools and efective treatments.

 Heterogeneous disease: small cell lung carcinoma

(SCLC, 20%, derived from neuroendocrine cells) and
non-small cell carcinomas (NSCLC, 80%, derived from
alveolar epitelial cells). Most common subtype:
adenocarcinoma.

 Risk factors: smokers have a 10-fold increased risk

(85% of cases are associated with smoking).

 Other carcinogens: asbestos, arsenic, air pollution,

radon; susceptibility genes (p.e., CYP1A1).

 Signs and symptoms: cough, weight loss, hemoptisis,

dyspnea, chest pain.
Lung Cancer
The identification of activating mutations in signal
transduction pathways that are central in cancer
pathophysiology has provided new therapeutic targets!

Targeted therapies and Personalized Medicine:

EGFR inhibitors are efficacious in EGFR-
mutant, NSCLC patients!
 Colorectal Cancer
 Cancer of the large intestine (colon), or in the last several
inches of the colon (rectal).

 Ranging from benign polyps and adenomas to invasive

cancer, and are predominantly epithelial-derived tumors
(adenocarcinomas).

 Risk factors: age, familiar history of polyps/colon cancer,

rare inherited gene mutations (i.e. APC, MLH1, STK11,
MUTYH), diet factors (high-fat/low-fiber), diabetes, obesity,
smoking, alcohol.

 Signs and symptoms: change in bowel habits (longer than

a month), blood in feces, abdominal discomfort/pain,
weakness/fatigue, weight loss…

 Acquired gene mutations: KRAS, TP53, SMAD4, APC...