For MMC-CN Students. Lectured by Prof. Julius Floresta.

1. 2. CELLULAR ABERRATION
The Biology of Cancer
Prof. Flas Julius Flores

2. TERMS
 Cancer – a disease process that begins when an
abnormal cell is transformed by the genetic mutation of
the cellular DNA
 In cancer, the abnormal cell forms a clone and begins to
proliferate abnormally, ignoring growth-regulating signals
in the environment surrounding the cell
 Hyperplasia
 Metaplasia
 Dysplasia
 Anaplasia
 Neoplasia – new growth; tumor; can be benign or
malignant; uncontrolled cell growth that follows no
physiologic demand

3. TERMS
 Benign – not malignant; an abnormal growth that is
stable, treatable and generally not life-threatening
 Malignant – cancerous; cells that are invasive and
tend to metastasize, uncontrollable or resistant to
therapy; rapidly spreading
 Invasion – refers to the growth of the primary tumor
into the surrounding host tissues
 Metastasis – the dissemination or spread of
malignant cells to distant sites by direct spread of
tumor cells to body cavities or through lymphatic
and blood circulation

4. Characteristics of Benign and Malignant Neoplasms
Characteristics Benign Malignant
Cell characteristics Well-differentiated that Cells are undifferentiated
resemble normal cells of and often bear little
the tissue from which the resemblance to the
tumor originated normal cells of the tissue
from which they arose
Grows at the periphery
and sends out processes
Mode of growth Tumor grows by that infiltrate and destroy
expansion and does not the surrounding tissues
infiltrate the surrounding
tissues; usually Variable and depends on
encapsulated level of differentiation; the
more anaplastic the
Rate of growth Usually slow tumor, the faster its
growth

5. Characteristics of Benign and Malignant Neoplasms
Characteristics Benign Malignant
Metastasis Negative Gains access to the blood
and lymphatic channels and
metastasizes to other areas
of the body
Often causes generalized
General effects Is usually a localized effects, such as anemia,
phenomenon that does not weakness, and weight loss
cause generalized effects
unless its location interferes
with vital functions
Often causes tissue damage
Does not usually cause as the tumor outgrows its
Tumor destruction tissue damage unless its blood supply or encroaches
location interferes with blood on blood flow to the area;
flow may also produce
substances that cause cell
damage
Does not usually cause
Ability to cause death death unless its location Usually causes death unless
interferes with vital functions growth can be controlled

13. TERMS
 Carcinoma – term used for malignant tumors of
epithelial in origin (bronchogenic carcinoma,
invasive ductal carcinoma, endometrial carcinoma,
adenocarcinoma, squamous cell carcinoma, basal
cell carcinoma)
 Sarcoma – term used for malignant tumors of
mesenchymal/connective tissue in origin
(rhabdomyosarcoma, liposarcoma,
leiomyosarcoma, angiosarcoma)
 Note: benign tumors usually end with the suffix
“oma”, except for lymphoma, hepatoblastoma,
neuroblastoma, myeloma, melanoma. These are
already malignant

14. TERMS
 Solid tumor – an abnormal mass that does not
contain cyst or liquid.
Example of conditions : breast cancer, colorectal ,
neuroblastoma, Wilms tumor, uterine, brain, lung
cancer
 liquid – mass that contain liquid.
Example: Lymphomas ( Hodgkin and non- Hodgkin),
leukemia

16. Fibroadenoma – solid
tumor
Fribrocystic change, breast –
cystic/liquid tumor

18. TERMS
 Angiogenesis – the growth of new capillaries from
the host tissue by the release of growth factors and
enzymes such as vascular endothelial growth factor
(VEGF)
 Mutation – an alteration in a DNA nucleotide
sequence – the order of the four bases adenine (A),
cytosine (C), thymine (T), and guanine (G)
 Mutations can alter both the sequence of a gene
and its regulatory sites
 Tumor suppressor genes – normally suppress or
negatively regulate cell proliferation by encoding
proteins that block the action of growth-promoting
proteins

20. TERMS
 DNA-repair genes – the “caretaker genes” – genes
involved in controlling or regulating genetic
instability to ensure integrity of genetic information
 Oncogenes – genes that encode proteins
(oncoproteins) whose action promotes cell
proliferation

21. TUMOR SUPPRESSOR GENES
 Hallmark characteristic of a mutated tumor
suppressor gene is loss of function through:
1. Loss of genetic material
2. Loss of information
 Examples:
a. APC, MEN1, p53, RB, and WT1 – affect DNA
transcription
b. BRCA1 and BRCA2 – play roles in DNA repair
c. RB, p16 and TP53 – critical for the operation of
the cell cycle, suggesting that many tumor
suppressor genes act as “gatekeeper” genes

28. SOME EXAMPLES OF GENES IN CANCER
SUSCEPTIBILITY
 ALDH2 – alcohol-related cancers
 APC – colorectal cancer
 CCND1 – head and neck cancer
 COMT – breast cancer
 CYP1A1 – lung, oral, and breast cancers, childhood
leukemias
 GSTM1 - bladder and breast cancers; lung cancers
 HRAS – breast, ovarian, lung and colorectal cancer
risk
 LTA – myeloma
 MCIR – melanoma

29. THEORIES AND RESEARCH MODELS OF TUMOR
DEVELOPMENT
Key Points of Major of Tumorgenesis
Theory Key Points
Multistep Initiation:
•Stem cell becomes initiated by acquiring one or more
mutations, leading to partial escape from normal homeostatic
control
•Genetic mutations or epigenetic events responsible
•Irreversible
Promotion
•Initiated cell stimulated to proliferate but not terminally
differentiate
•Initiated cell acquires further genetic changes required for
neoplasms
•Interruptible and sometimes reversible
Progression
•Malignant conversion of cell
•Confers autonomous growth of initiated cell
•Irreversible

30. THEORIES AND RESEARCH MODELS OF TUMOR
DEVELOPMENT
Key Points of Major of Tumorgenesis
Theory Key Points
Mutagenic Mutagenesis
versus •Results in qualitative or quantitative alteration information
epigenetic •Chronic insults produce two to three mutations in individual
cells within particular tissues
•These mutations initiate tumors
Epigenetic process
•Chronic insults repeatedly injure and transiently excite many
cells in particular tissues
•These insults alter expression of genetic information at the
transcriptional, translational, or posttranslational levels
•Mutations are secondary events

31. THEORIES AND RESEARCH MODELS OF TUMOR
DEVELOPMENT
Key Points of Major of Tumorgenesis
Theory Key Points
Nature versus Mutagens found in the environment (nurture) must interact with
nurture DNA (germ or somatic cell) to induce mutations un genes
affecting cancer progress directly (e.g., oncogenes/tumor
suppressor genes) or indirectly (e.g., DNA repair genes, growth
factors)
Oncogene and Oncogenes: Do not contact inhibit; do not terminally differentiate
tumor or undergo apoptosis
suppressor Tumor suppressor genes: When mutated, do not stop unregulated
gene cell growth, induce differentiate, or undergo apoptosis
Stem cell
Stem cell versus •Pluripotent stem cells restricted to allow a finite number of cell to
de- only specific lineage of cell types within the organs that arise from
differentiation the stem cells
•Daughter (progenitor) cells of these pluripotent stem cells would
give rise to terminally differentiated cells of that lineage
Dedifferentiation: Some progenitor cells could revert back to a
pluripotent cell

33. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Cytological changes Increased size and Reflects greater activity of
number of nucleoli tumor cells
Increased Larger nucleus reflects
nuclear/cytoplasmic ratio more activity, more
Altered cytoskeleton genetic information
Changes contribute to
increased mortality and
variable sizes and shapes
(pleomorphism)
Immortality
Altered cell growth Normal cells senesce
(ramian viable but do not
divide)
During a crisis, cells
mature, proliferate
indefinitely, become
“immortal”

34. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Altered cell growth Immortality Telomeres (DNA
segments at the ends of
chromosomes) limit the
number of cell doublings.
Telomeres shorten with
each chromosomal
replication until reaching a
threshold at which cells
senesce. Telomere
stability is critical for
cancer progression. Many
cancer cells contain
telomerase, an enzyme
that prevents telomere
shortening and enables
the cell to replicate
indefinitely

35. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Altered cell growth Decreased density- Normal cells stop growing
dependent growth when they contact other
inhibition (loss of contact cells crowding from
inhibition) contact compromises
access to nutrients
Transformed cells do not
respond to physical
contact and with chemical
signals from neighboring
cells, thereby continue to
grow beyond normal limits
Loss of contact inhibition
may result from a faulty
restriction point

36. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Altered cell growth Decreased requirement Serum normally provides
for serum growth factors necessary
for cell development and
survival
Typically, the growth
factor binds to a receptor
on the cell surface, which
in turn activates the
intracytoplasmic portion of
the receptor to send a
message to the nucleus
(signal transduction),
where an effect on gene
function occurs.

37. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Altered cell growth Decreased requirement Sometimes, an abnormal
for serum growth factor receptor on
the surface of cancer or
transformed cell can
activate the signal
pathway spontaneously
without exposure to
growth factor
Cancer and transformed
cell lines may grow in
media without serum,
suggesting that they can
synthesize and secrete
their own growth factors
(autocrine stimulation)

38. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Altered cell growth Loss of anchorage- Cells require a substance
dependent growth to grow. Transformed
cells do not require a solid
substrate
Only tumor cells grow in
soft agar (no anchorage);
cell growth in soft agar is
highly correlated with
tumorigenicity
Loss of cell cycle control Cell does not progress
normally through cell-
cycle pathways and
checkpoints
Reduced apoptosis Cancer cells are less
susceptible to
programmed cell death

39. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Changes in cell New surface antigens Cancer and transformed
membrane cells exhibit new
molecules on the surface
Viruses can transform
and alter multiple cell-
surface antigens
New or altered Transformed cells usually
glycoproteins (proteins have profound changes in
with polysaccharides) cell-surface glycoproteins
Some changes may alter
cell-cell and cell-matrix
adhesions
Mechanism by which
polysaccharides are
made and attached to
protiens is deranged in
transformed cells

40. Properties of Cancer
Property Characteristics of Cancer Explanation
and Transformed Cells
Changes in cell New or altered glycolipids Content and complexity of
membrane glycolipids are reduced in
transformed cell membranes
Glycosphingolipid interacts
with receptor proteins on the
surface of normal cells to
inhibit their responsiveness
to growth factors
Transformed cells have less
and/or altered
glycosphingolipids on their
cell surfaces, increasing their
responsiveness to growth
factors. Glycosphingolipids
also serve as components of
surface markers involved in
normal cell growth

41. THE CELL CYCLE

42. THE CELL CYCLE
 A malfunction of any of these regulators of cell
growth and division can result in the rapid
proliferation of immature cells
 In some cases these proliferating immature cells
are considered cancerous (malignant)
 Knowledge of the cell cycle events is used in the
development of chemotherapeutic drugs, which are
designed to disrupt the cancer cells during different
stages of their cell cycle

45. CARCINOGENESIS
 Three-step process
1. Initiation – initiators (carcinogens), such as
chemicals, physical factors, and biologic agents
escape normal enzymatic mechanisms and alter
the genetic structure of the cellular DNA
2. Promotion – repeated exposure to promoting
agents causes the expression of abnormal or
mutant genetics information
3. Progression – the altered cells exhibit increased
malignant behavior; they now have the propensity
for invasion and metastasis

46. CARCINOGENESIS
 Etiology
a. Viruses and bacteria
b. Physical agents
c. Chemical agents
d. Genetics and familial factors
e. Dietary factors – fats, alcohol, salt-cured or
smoked meats, nitrate-containing and nitrite
containing foods, red and processed meat
f. Hormonal agents – DES, OCP and prolonged
progesterone therapy

47. DIETARY FACTORS
 Alcohol increases the risk of cancers of the mouth,
pharynx, larynx, esophagus, liver, colorectum, and
breast
 Greater consumption of vegetables and fruits is
associated with decreased risk of lung, esophageal,
stomach, and colorectal cancers
 High caloric dietary intake is also associated with
an increased cancer risk
 Obesity is clearly associated with endometrial
cancer, postmenopausal breast cancers, and colon,
esophagus, and kidney cancers, as wells as
pancreatic cancer, gallbladder, thyroid, ovary,
cervix, prostate cancer, and multiple myeloma

48. GRADING VERSUS STAGING
 Grading – identification of the type of tissue from
which the tumor originated and the degree to which
the tumor cells retain the functional and structural
characteristics of the tissue of origin
 Staging – process of determining the extent of
disease, including tumor size and spread or
metastasis to distant sites
 TNM Staging
T – primary tumor
N – regional nodal metastasis
M – distant metastasis

49. TNM CLASSIFICATION SYSTEM
 Primary tumor
Tx – Primary tumor cannot be assessed
T0 – No evidence of primary tumor
Tis – carcinoma in-situ
T1, T2, T3, T4 – increasing size and/or local extent of the
primary tumor
 Regional lymph node metastasis
Nx – Regional LN cannot be assessed
N0 – No regional LN metastasis
N1, N2, N3 – Increasing involvement of regional LN
 Distant metastasis
Mx – Distant metastases cannot be assessed
Mo – No distant metastases
M1 – Distant metastases

58. CANCER WARNING SIGNS AND SYMPTOMS
 C change in bowel habits sign of colorectal cancer
 A sore that does not heal on the skin or in the mouth
could be malignant
 Unusual bleeding or discharge from rectum, bladder or
vagina could be colorectal, prostate, bladder or cervical
cancer
 Thickening of breast tissue or a new lump in breast
 Indigestion or trouble swallowing cancer of the mouth
throat esophagus or stomach.
 Obvious changes to moles or warts could be skin cancer
 Nagging cough or hoarseness that persists for four to
six weeks could be cancer of lung or throat cancer.

59. OTHER MANIFESTATIONS OF CANCER
 Impaired immunity
 Hemorrhage
 Anemia
 Anorexia-cachexia syndrome
 Paraneoplastic syndromes – indirect effects of
cancer
a. Breast, ovarian, and renal cancers may set up
ectopic parathyroid hormone sites, causing severe
hypercalcemia
b. Oat cell and lung cancers may produce ectopic
secretions of insulin, PTH, ADH, and ACTH
 Pain

60. OTHER MANIFESTATIONS OF CANCER
 Physical stress – when the immune system
discovers a neoplasm, it tries to destroy it using the
resources of the body
 Psychologic stress

66. ROLE OF THE NURSE
 caregiver
 advocate
 case manager
 educator
 change agent
 counselor
 educator
 epidemiologist