What is cancer?

• Caner is defined as the continuous

uncontrolled growth of cells.
• A tumor is a any abnormal
proliferation of cells.
• Benign tumors stays confined to its
original location
• Malignant tumors are capable of
invading surrounding tissue or
invading the entire body
• Tumors can arise from any cell type
in the body
Abnormal cell growth (neoplasia)
Benign: slow growth, non-invasive, no metastasis
Malignant: rapid growth, invasive, potential for metastasis

Is cancer a heritable disease?

There are heritable cancer syndromes. The majority of cancers, however, are not
familial. Cancer is a genetic disease, but the majority of mutations that lead to
cancer are somatic
Normal Cells vs. Cancer Cells
 The Vocabulary
• Hyperplasia – increased number of cells
• Hypertrophy – increased size of cells
• Dysplasia – disorderly proliferation
• Neoplasia – abnormal new growth
• Anaplasia – lack of differentiation
• Tumor – originally meant any swelling, but now equated with neoplasia
• Metastasis –growth at a distant site
 Classification of Neoplasms
• Benign Tumor (-oma)
• Adenoma (“adeno-” means gland-like)
• Fibroma
• Lipoma (“lipo-” means fat)

• Malignant Cancer (carcinoma or sarcoma)

• Adenocarcinoma
• Fibrosarcoma (“sar-” means fleshy)
• Liposarcoma
• Leukemia and Lymphoma
 Types of Cancers by Origin
• Epithelial:
• Carcinomas; constitute 90% of cancers, are cancers of epithelial cells
• Mesenchymal
• Sarcomas; are rare and consist of tumors of connective tissues (connective
tissue, muscle, bone etc.)
• Hematopoietic (Blood Cancer): constitute 8% of tumors. Sometimes referred to
as liquid tumors.
• Leukemias are a group of cancers that affect the blood and bone marrow. All
leukaemias start in the bone marrow where developing blood cells, usually
developing white cells, undergo a malignant (cancerous) change.
• Lymphomas arise from cells of the immune system (T and B cells).
Lymphomas are cancers of the lymphatic system. Lymphomas arise when
developing lymphocytes undergo a malignant (cancerous) change and multiply
in an uncontrolled way.
• Myeloma, or multiple myeloma, is a cancer of plasma cells. Plasma cells are
mature B-lymphocytes that live predominantly in the bone marrow and
normally produce antibodies to help fight infection. In myeloma, plasma cells
undergo a malignant (cancerous) change and multiply in an uncontrolled way
causing problems in different parts of the body. Large numbers of abnormal
plasma cells, called myeloma cells, collect in the bone marrow and may
interfere with blood cell production and damage the adjacent bones causing
pain. Myeloma cells produce an abnormal type of antibody called paraprotein
that can usually be detected in blood and/or urine.
 Most malignant cells become metastatic
Invade surrounding tissue and establishment of secondary areas of
growth: Metastasis
 Predictors of Behavior
• Grade – How bad do the cells look?
• The pathologist gives the cancer a grade based on how different they look from
normal cells (differentiation), how quickly they are growing and dividing, and how
likely they are to spread. (How aggressive is the cancer?)
• Stage – Where has the cancer spread?
• Tumor (Size of Tumor)
• Nodes (degree of spread to regional lymph nodes)
• Metastasis (if cancer has spread to other body parts)

Staging is a way of describing

or classifying a cancer based
on the extent of cancer in the
body. The stage is often
based on the size of the
tumour, whether the cancer
has spread (metastasized)
from where it started to other
parts of the body and where it
has spread.
Grading Cancer
 What causes the mutations that lead to cancer?

• Chemical Exposure
• Tobacco smoke
• Environmental (PCBs)
• Occupational (coal tar, asbestos, aniline dye)
• Diet (aflatoxin)
• Radiation (UV, ionizing)
• Infection
• Viruses (EBV, hepatitis B, papilloma)
• Bacteria (Helicobacter)
• Inherited familial cancer syndromes

What do these agents have in common?

Viruses: insertional mutagenesis
Chemicals: DNA adducts
UV and ionizing radiation: single and double strand DNA breaks
What causes Cancer?
Genetic mutations
Chromosomal Instability
 Phenotype of a cancer cell: The Six Hallmarks of Cancer
• Self-sufficient growth signals
• Constitutively activated growth factor signalling

• Resistance to anti-growth signals

• Inactivated cell cycle checkpoint

• Immortality
• Inactivated cell death pathway

• Resistance to cell death

• Activated anti- cell death signalling

• Sustained angiogenesis signalling (Angiogenesis is the formation of new

blood vessels)
• Activated VEGF (Vascular Endothelial Growth Factor Receptors,
VEGFs) are master regulators of vascular development and of blood and
lymphatic vessel function during health and disease in the adult)
• Invasion and metastasis
• Loss of cell-to-cell interactions, etc.
 What types of genes get mutated in cancer?
• Oncogenes are activated
• Normal function: cell growth, gene transcription
• Tumor suppressor genes are inactivated
• Normal function: DNA repair, cell cycle control, cell death
Types of proteins encodes by oncogenes
 Tumor suppressors
• “Guardian(s) of the genome”
• Often involved in maintaining genomic integrity (DNA repair, chromosome
segregation)
• Mutations in tumor suppressor genes lead to the “mutator phenotype”—mutation
rates increase
• Often the 1st mutation in a developing cancer

p53—a classic tumor

suppressor