CANCER AND CANCER

BIOLOGY: REVIEW
ALVYN KLEIN A. MANA-AY, MPH, MSc, RND
Assistant Professor, HE-Nutrition and Dietetics Department
College of Education, Silliman University
BACKGROUND: WHAT IS CANCER?
➤ Group of diseases including solid tumors in nearly all tissues, and
leukemias.
➤ CA: disease of the body’s own cells
➤ Cellular features:
➤ uncontrolled cell division
➤ change in morphology
➤ de-differentiation

➤ cell migration into adjacent and distant tissues

BACKGROUND: WHAT IS CANCER?
➤ Normal cells divide only when a signal is received, and
inhibited from dividing at the wrong time.

➤ Normal cells undergo apoptosis in response to damage or

normal aging.

➤ CA cells develop from normal cells via a series of mutations to

genes involved in cell division control
CHARACTERISTICS OF CANCER CELLS

➤ uncontrolled growth
➤ altered biochemistry
➤ loss of contact
inhibition resulting in
foci formation
➤ immortality
“SEED AND SOIL” IN CANCER BIOLOGY

➤ “SEED” are the

transformed cells that
has been mutated
➤ “SOIL” is the
environment or the
surrounding tissues
CANCER HISTOPATHOLOGY

CLASSIFICATION TISSUE ORIGIN COMMON TYPES

breast, prostate, liver,

Carcinoma Epithelial
lung, pancreas, colon

Sarcoma Connective tissue bone, cartilage, fat, nerve

Lymphoma and Leukemia Hematopoetic leukemia

Germ cell Pluripotent cells testicle, ovary

Immature precursor cells

Blastoma
or embryonic tissue
METASTASIS
SOMATIC MUTATION THEORY
➤ CA arises as a result of genetic abnormalities or
mutations
➤ Characteristichallmarks are gradually acquired through
accumulation of genetic mutations
➤ CA is associated with exposure to carcinogenic stimuli:
➤ mutagenic initiating agents
➤ non-mutagenic promoting agents
`
IARC CLASSIFICATION OF HUMAN CARCINOGENS
IARC CLASSIFICATION OF HUMAN CARCINOGENS
THE FATE OF CHEMICAL CARCINOGENS IN THE BODY
➤ Most chemical are biotransformed
➤ Most biotransformations produce stable, detoxified, more
hydrophilic products
➤ Some biotransformations are bioactivations producing
reactive, toxic, and/or carcinogenic
➤ Bioactivated intermediates react with DNA, RNA, proteins,
and other critical cellular molecules - mutations, cell
alterations, cytotoxicity
BIOTRANSFORMATION VIA CYP450 ENZYMES
BIOTRANSFORMATION VIA CYP450 ENZYMES
➤ P450 bioactivates chemicals to
electrophilic (electron-loving)
intermediates that react with
critical cellular nucleophiles
(nucleus-loving), such as DNA,
RNA, proteins, etc., resulting to
toxicity and cancer
➤ Pro-carcinogens (e.g. benzene,
styrene, nitrosamines, aflatoxin,
benzo-a-pyrene, vinyl chloride)
ERRORS CAUSED BY DNA ADDUCTS LEADING TO MUTATION
➤ base pairing
➤ cell cycle effects
➤ loss of cellular control
➤ gene regulation
➤ methylation patterns
➤ aberrant gene expression
➤ post transcriptional/translational processing
MECHANISM OF DNA ADDUCT FORMATION AND CANCER
WHAT IS A MUTATION?
➤ An early event in
carcinogenesis
➤ Change to the DNA sequence
passed on when a cell
replicates
➤ Mutations arise spontaneously
but more likely when DNA is
damaged or chemically
modified
EPIGENETIC CHANGES IN CANCER
INITIATOR VS. PROMOTER
 Chemical Exposure

MULTISTAGE TUMOR PROGRESSIONBioactivation

Clinical Tumor

Initiation

Promotion and Progression

WEINBERG’S HALLMARKS OF CANCER
THE INTEGRATED CELL CIRCUIT OF THE CELL
ONCOGENES AND TUMOR SUPPRESSOR GENES

➤ Mutations in a relatively few genes are critical to

carcinogenesis and tumor development
➤ These genes are known as oncogenes and tumor
suppressor genes
ONCOGENES

➤ Proto-oncogenes: control cell growth and division

➤ Become oncogenes when mutated or activated
➤ Oncogenes dominantly act as transforming genes
(mutation in only one copy of gene is sufficient)
➤ Activated oncogenes lead to uncontrolled cell division
RAS ONCOGENE

➤ “rat sarcoma”
➤ Most commonly implicated proto-oncogene in human
cancers
➤ Function in normal cells: intracellular signal
transduction
P53 GENE
➤ a.k.a. “Guardian of the Genome” or “Molecular Police”
➤ Defense gene: protective; prevent cells from becoming cancerous
➤ Inactivation (gene deletion, silencing, mutation) results to cancer
progression
➤ Functions:

➤ prevent cells from replicating if DNA is damaged (allowing time

for repair)
➤ triggers apoptosis (“cell suicide”) if DNA is too damaged to repair
THE INTEGRATED CELL CIRCUIT OF THE CELL