Pa Tho Physiology of Cancer

8/6/2019 Pa Tho Physiology of Cancer

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Pathophysiology of Cancer


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Characteristics of Cancer

M

olecularM

echanisms of GrowthControl

Cancer Genetics

Tumor/Host Interactions

Clinical Application: Breast Cancer


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The Nature of Cancer


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Neoplasia

Unregulated accumulation

of cells


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Normal Tumor

Abnormal regulation of cell growth

Abnormal cell-cell interactions


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Normal Tumor

Normal stem cell Cancer stem cell


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Characteristics of Stem Cells Unlimited capacity for self-renewal

Cellularimmortality

But relatively low rate of proliferation

Capable of differentiation into the maturecells that constitute organ function

Proliferation can be dramatic once a cell hascommitted to differentiation

But differentiated cells have limited life-span


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Etc., Etc., Etc.

Maturation

Compartment

Etc.

Maturation

Compartment

Stem cellCompartment

Proliferative

Compartment

Normal Cancer

Cell loss (apoptosis)


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Lessons From Stem Cell Kinetics

The growth rate of cancer cells does not

exceed that of normal cells

Abnormal differentiation of cancer cellsresults in a greater percentage of cells in the

proliferative pool (at the expense of the

maturation pool)

Tumor (mass) growth exceeds normal growth

due to a higher proliferative fraction and a

lower rate of cell loss (death)


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Benign Malignantpleomorphism

abnormal nuclei

mitoses

loss of polarity

abnormal differentiation


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Invasion


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Abnormal cell-substratum interaction


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Invasion into adjacent structures


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Dissemination (Metastases)


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Penetration of vasculature

Survival in circulation

Survival in a new organ


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metastatic spread is not random but determined by:-pattern of venous blood flow

-specific receptors on tumor and endothelial cells

-metastatic fitness is genetically determined


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CancerE

pidemiology

Or,

Guilt by Association


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Caveat epidemiology Studies are observational and therefore

do not establish cause and effect

Initial observations require confirmation

and exclusion of confounding variables

However, well-performed studies can

provide valuable insights into factors

that contribute to cancer.


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Cancer Incidence Cancer is a disease of aging

Deaths increased 3x in the 7th decade

compared to the 5th & 6th decades combined

But, cancers differ in their age-relatedincidence


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Cancer Incidence Environment affects cancer incidence

Differences in the incidence of breast, liver,

gastric, colon and prostate cancers inJapanese and US populations disappearfollowing immigration (unknown factors)

Liver cancer incidence is related to incidenceof Hepatitis B &C incidence and afflatoxinexposure

Melanoma incidence is associated with UVexposure


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Cancer Incidence Toxins affect cancer incidence

Tobacco - lung, upper aerodigestive tract &

everything else Asbestos - lung, mesothelioma

Alcohol - liver, upper aerodigestive tractesophagus,

Others - see table 7-3


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Cancer Incidence Infectious agents

H. pylori - gastric lymphoma & adenoCA

Papillomavirus - cervical CA

HTLV - T-cell leukemia

Epstein-Barr virus - lymphomas andnasopharyngeal cancers


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Cancer Incidence Genetic factors

Specific cancer genes (addressed later)

Unidentified genetic factors (generally alow level familial risk)


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Cancer Incidence Obesity increases the risk of most

cancers


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CancerEpidemiology

Conclusions

Cancer is the result of the cumulative effects

of living and the interplay of environmentalexposures and genetic predisposition

It is likely that most risk factors act as either

Initiators orPromoters of carcinogenesis.

Pa Tho Physiology of Cancer

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