Sunday, 26 January 2020

ONCOLOGY

BASIC TERMINOLOGIES

- Incidence

• number of new cases per 100,000 persons per year

- Deaths

• number of deaths per 100,000 persons per year

- Cohort studies

• initially do not have a disease over time and measure the rate of development of a
disease.

• usually is compared to a group that has not been exposed

- Case control

• group of patients affected with a disease to a group of individuals without the

disease and looks back retrospectively to compare how frequently the exposure to
a risk factor is present in each group to determine the relationship between the risk
factor and the disease

• relative risk <1 indicates a protective effect of the exposure, whereas a relative risk
>1 indicates an increased risk of developing the disease with exposure.

- Top 5 malignancies

• Males: lung, prostate, colorectal cancer, stomach, and liver

• Females: breast, colorectal, cervix, lung, and stomach

CANCER BIOLOGY

- Alterations in physiology

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• self-sufficiency of growth signals, insensitivity to growth-inhibitory signals, evasion
of apoptosis, potential for limitless replication, angiogenesis, and invasion and
metastasis, reprogramming of energy metabolism and evading immune
destruction

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ONCOGENES

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- myc or ras

- Her2

• member of the epidermal growth factor receptor (EGFR)

• breast, ovarian, lung, gastric, and oral cancers

APOPTOSIS

- chromatin condensation, nuclear fragmentation, and DNA laddering, membrane

blebbing

- caspases

• effectors of apoptosis

• initiator caspases (e.g., 8, 9, and 10) and executioner caspases (e.g., 3, 6, and 7)

CANCER GENOMICS

- most common class of genomic alterations —> chromosomal translocation —>

chimeric gene.

- most common cancer genes are protein kinases.

HEREDITARY CANCER RISK

- Factors:

• Younger age than usual

• Presence of bilateral disease

• Presence of multiple primary malignancies

• Presentation of a cancer in the less affected sex (e.g., male breast cancer)

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• Clustering of the same cancer type in relatives

• Occurrence of cancer in association with other conditions such as mental

retardation or pathognomonic skin lesions

- rb1

• retinoblastoma gene

• at risk for developing a midline intracranial tumor, most commonly pineoblastoma.

- p53 and Li-Fraumeni syndrome

• early-onset breast cancer, soft tissue sarcomas, brain tumors, adrenocortical

tumors, and leukemia

• classic LFS
- bone or soft tissue sarcoma <45 years

- first-degree relative with cancer <45 years,

- another first- or second-degree relative with either a sarcoma diagnosed at any

age or any cancer diagnosed <45 years.

- BRCA1 and BRCA2

• BRCA1
- breast cancer (87%) and ovarian cancer (44%)

- colon and prostate CA

• BRCA2
- breast cancer (84%) and ovarian cancer (27%)

- prostate, gallbladder, pancreatic, gastric, melanoma CA

• male breast CA = BRCA2

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- APC

• with familial adenomatous

polyposis (FAP)

• upper intestinal
neoplasms, hepatobiliary
tumors, thyroid
carcinomas, desmoid
tumors, and
medulloblastomas

- HNPCC

• as Lynch syndrome
- type 1: predisposition for colorectal cancer with early age of onset
(approximately age 44 years) and an excess of synchronous and metachronous
colonic cancers

- type 2: similar colonic phenotype accompanied by a high risk for carcinoma of

the endometrium, transitional cell carcinoma of the ureter and renal pelvis, and
carcinomas of the stomach, small bowel, ovary, and pancreas

• microsatellite instability
- PTEN

• autosomal dominant syndrome Cowden disease (CD) or multiple hamartoma

syndrome

• with an increased risk of breast and thyroid cancers.

- p16

• malignant melanoma
- e-cadherin

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• Hereditary diffuse gastric carcinoma
- RET

• medullary thyroid carcinoma

• multiple endocrine neoplasia type 2 (MEN2) syndromes

• MEN2A
- medullary thyroid carcinoma and pheochromocytoma (in 50%) or parathyroid
adenoma (in 20%),

• MEN2B
- with medullary thyroid carcinoma, marfanoid habitus, mucosal neuromas, and
ganglioneuromatosis of the gastrointestinal tract.

CHEMICAL CARCINOGENS

- genotoxins: initiate carcinogenesis by causing a mutation

- cocarcinogens: by themselves cannot cause cancer but potentiate carcinogenesis by

enhancing the potency of genotoxins.

- tumor promoters: enhances tumor formation when given after exposure to

genotoxins.

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VIRAL
CARCINOGENS

ANTICANCER AGENTS

- Alkylating agents

• cell-cycle– nonspecific agents

• cross-linking the two strands of the DNA helix or by causing other direct damage to
the DNA

• classic alkylators, nitrosoureas, and miscellaneous DNA-binding agents

- Antitumor antibiotics

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• products of fermentation of microbial organisms

• cell-cycle nonspecific.

• interfering with DNA or RNA synthesis,

- Antimetabolites

• cell-cycle– specific

• major activity during the S phase and a little effect on cells in G0

• they interfere with normal synthesis of nucleic acids by substituting for purines or
pyrimidines in the metabolic pathway to inhibit critical enzymes in nucleic acid
synthesis

- Plant alkaloids

• from periwinkle plant (Vinca rosea), or the root of American mandrake, Podophyllum
peltatum

• vinca alkaloids: by binding to tubulin in the S phase —> blocks microtubule

polymerization —> impaired mitotic spindle formation in the M phase.

• Taxanes: cause excess polymerization and stability of microtubules —> blocks the
cell cycle in mitosis.

• epipodophyllotoxins (e.g., etoposide): inhibit a DNA enzyme (topoisomerase II)

.—> stabilizing the DNA-topoisomerase II complex —> inability to synthesize DNA
—> cell cycle is stopped in the G1 phase.

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RADIATION THERAPY

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