CANCER (NEOPLASIA) — DETAILED EXAM-

STANDARD SYNOPSIS
Mechanism-focused, high-yield, fully explained with clear flow and connections (no
omissions)

1. NORMAL CELL GROWTH vs CANCER

Normal cellular behavior

Under physiological conditions, body cells exhibit strict regulation of growth, involving:

 Controlled proliferation (cell division)

 Differentiation (specialization)
 Apoptosis (programmed cell death)

These processes occur in a coordinated, sequential, and balanced manner, ensuring tissue
integrity.

Definition of Cancer

 Cancer is a condition characterized by:

o Loss of control of cell growth
o Uncontrolled proliferation
o Ability to invade and spread (metastasis)

Origin of the term

 Derived from Latin word “crab”

 Reflects:
o Ability of cancer cells to spread and cling
o Associated pain and invasive behavior

2. NEOPLASIA AND TUMOR CLASSIFICATION

Neoplasia
  Literal meaning: “new growth”
 Refers to abnormal, uncontrolled cell proliferation

Tumor

 Originally meant swelling

 Now refers to mass of proliferating cells

Oncology

 Study of tumors (oncos = tumor)

3. TYPES OF TUMORS

1. Benign Tumors

Characteristics

 Grow by expansion
 Surrounded by capsule (connective tissue)
 Localized
 Do NOT invade surrounding tissues

Clinical significance

 Usually not life-threatening

Examples

 Moles
 Warts

2. Malignant Tumors (CANCERS)

Characteristics
  Uncontrolled proliferation
 Invasion of surrounding tissues
 Ability to spread → metastasis

Metastasis (VERY IMPORTANT)

 Spread of cancer cells from:

o Primary site → distant organs
 Leads to:
o Secondary tumors
 Major cause of:
o Morbidity and mortality

Types based on origin

 Carcinomas → epithelial origin

 Sarcomas → connective tissue origin

4. INCIDENCE AND EPIDEMIOLOGY

 Cancer = second leading cause of death (after coronary heart disease)
 Accounts for >20% of deaths in developed countries
 Lifetime risk:
o ~ 1 in 3 individuals

Age distribution

 70% cases occur in >60 years

 Also significant in children:
o Especially leukemia (age 3–13)

Preventable factors (~90% cases)

 Tobacco
 Alcohol
  Diet
 Pollution
 Occupational exposure

5. ETIOLOGY (CAUSES OF CANCER)

Cancer is multifactorial:

1. Chemical carcinogens

2. Radiation

3. Viruses

4. Genetic factors

6. CHEMICAL CARCINOGENS (VERY HIGH-YIELD)

Contribution

 ~80% of cancers

Types

Organic

 Benzo(a)pyrene
 Dimethylbenzanthracene
 Nitrosamines

Inorganic

 Arsenic
 Cadmium
Sources of exposure

1. Occupation → asbestos, benzene

2. Diet → aflatoxin (fungal toxin in peanuts)
3. Drugs → diethylstilbestrol
4. Lifestyle → smoking

Mechanism of carcinogenesis

Step 1: Activation (VERY IMPORTANT)

 Many carcinogens are procarcinogens (inactive)

 Activated by:
o Cytochrome P450 system

Step 2: Formation of ultimate carcinogen

 Reactive intermediate capable of binding DNA

Step 3: DNA damage

 Covalent binding to:

o Purines
o Pyrimidines
o Phosphodiester backbone

Step 4: Mutation

 Changes in DNA sequence → mutagenesis

Step 5: Cancer development

 Accumulated mutations → uncontrolled growth

Key concept

 Chemical carcinogens are often mutagens

7. AMES TEST (CARCINOGEN SCREENING)

Principle

 Uses mutant strain of Salmonella typhimurium (His⁻)

Mechanism

 Cannot synthesize histidine → requires it externally

 Carcinogen exposure → reverse mutation → His⁺

Interpretation

 Growth without histidine → carcinogenic potential

Importance

 Detects ~90% carcinogens

 Used as screening test, followed by animal studies

8. PROMOTERS OF CARCINOGENESIS

Definition

 Substances that enhance carcinogenesis but are not carcinogenic alone

Example

 Benzo(a)pyrene (initiator) + Croton oil (promoter) → tumor

Key concept

 Cancer development often involves:

o Initiation + Promotion

9. RADIATION-INDUCED CANCER

Types

 UV rays
 X-rays
 Gamma rays

Mechanism

 DNA damage

UV radiation

 Causes pyrimidine dimers

X-rays / gamma rays

 Generate free radicals

Outcome

 Mutations → carcinogenesis
10. VIRAL CARCINOGENESIS

Historical discovery

 Demonstrated by Rous (1911)

Types of oncogenic viruses

RNA viruses (retroviruses)

 Leukemia
 Sarcoma

DNA viruses

 Epstein-Barr virus
 Papilloma virus

Mechanism

 Integration into host genome

 Expression of oncogenes
 Production of reverse transcriptase

11. DNA: CENTRAL ROLE IN CANCER

Evidence

1. Cancer cells produce identical daughter cells

2. Chromosomal abnormalities present
3. DNA mutations lead to cancer
4. Oncogenes can transform normal cells
Key concept

 Cancer = genetic disease of a single cell (monoclonal origin)

12. GENETIC BASIS OF CANCER

Three major gene categories:

1. Oncogenes
2. Antioncogenes (tumor suppressor genes)
3. Apoptosis-regulating genes

13. ONCOGENES

Definition

 Genes that promote cancer development

Origin

 Derived from normal genes:

o Proto-oncogenes

Function of proto-oncogenes

 Encode proteins regulating:

o Cell growth
o Division

Activation → oncogene → cancer

14. MECHANISMS OF ONCOGENE ACTIVATION

1. Viral insertion

 Retroviral DNA integrates into genome

 Activates proto-oncogene (e.g., myc)

2. Chromosomal translocation

Example: Burkitt’s lymphoma

 myc gene moved → overexpression

3. Gene amplification

 Increased copies of gene

 Example: dihydrofolate reductase (methotrexate resistance)

4. Point mutation

Example: ras gene

 Single base change → altered protein

15. MECHANISM OF ONCOGENE ACTION

Oncoproteins produced include:

A. Growth factors
  Stimulate cell proliferation

Mechanism

1. Bind receptor
2. Activate kinases
3. Phosphorylate proteins
4. Trigger cell division

B. Growth factor receptors

 Overexpression → excessive signaling

C. GTP-binding proteins (RAS) (VERY IMPORTANT)

Normal mechanism

 Ras inactive → GDP-bound

 Activation:
o GDP → GTP (via GRF)
 Active ras → stimulates kinases → cell division
 Deactivation:
o GTP → GDP (via GTPase + GAP)

Mutation effect

 Loss of GTPase activity

 Ras remains permanently active
 Continuous cell division → cancer

D. Non-receptor tyrosine kinases

  Phosphorylate proteins → stimulate growth
 Mutation → excessive activity

16. ANTIONCOGENES (TUMOR SUPPRESSOR GENES)

Function

 Inhibit cell proliferation

 Act as “brakes”

Example

 p53 gene

Loss leads to:

 Uncontrolled growth

Associated cancers

 Retinoblastoma
 Breast cancer
 Lung cancer

17. APOPTOSIS-REGULATING GENES

Example

 bcl-2
Function

 Prevents programmed cell death

Overexpression

 Cells survive abnormally

 Accumulate mutations → cancer

18. UNIFIED HYPOTHESIS OF CARCINOGENESIS

Sequence

Environmental factors (chemical, radiation, virus)

↓
DNA damage / mutation
↓
Activation of oncogenes
+
Loss of tumor suppressor genes
+
Failure of apoptosis
↓
Uncontrolled cell proliferation
↓
Cancer

19. TUMOR MARKERS

Definition

 Substances produced by tumor cells

Uses

 Diagnosis support
 Monitoring therapy
 Detect recurrence

Limitations

 Often not specific

Important examples

1. Carcinoembryonic antigen (CEA)

 Seen in:
o Colon
o Pancreas
o Lung
 Also elevated in non-cancer conditions

2. Alpha-fetoprotein (AFP)

 Liver cancer
 Testicular cancer
 Also increased in pregnancy, hepatitis

3. PSA

 Prostate cancer

20. CHARACTERISTICS OF CANCER CELLS

A. Morphological changes

 Rounded shape
 Altered cytoskeleton

Loss of contact inhibition

 Normal: monolayer growth

 Cancer: multilayer growth

Loss of anchorage dependence

 Grow without attachment

Increased motility

 Leads to metastasis

B. Biochemical changes

1. Increased DNA & RNA synthesis

→ rapid proliferation

2. Increased glycolysis (Warburg effect)

→ even in presence of oxygen

3. Reduced growth factor requirement

→ yet increased production

4. Fetal protein synthesis

 CEA, AFP

5. Altered membrane molecules

 Glycoproteins, glycolipids

21. METASTASIS (CRITICAL CONCEPT)

Definition

 Spread of cancer cells to distant sites

Mechanism (multifactorial)

 Loss of adhesion
 Increased motility
 Enzymatic degradation of tissues
 Vascular spread

22. CHEMOTHERAPY OF CANCER

Principle

 Targets rapidly dividing cells

Limitation
  Affects normal cells:
o Bone marrow
o GIT
o Hair follicles

Examples of drugs and mechanisms

Methotrexate

 Inhibits dihydrofolate reductase

 Blocks DNA synthesis

6-mercaptopurine

 Inhibits nucleotide synthesis

Actinomycin D

 Inhibits transcription

Vincristine/Vinblastine

 Inhibit spindle formation

Cisplatin

 Forms DNA crosslinks

23. PREVENTION OF CANCER

Antioxidants (VERY IMPORTANT)

  Vitamin E
 Vitamin C
 β-carotene
 Selenium

Mechanism

 Neutralize free radicals

 Reduce DNA damage
 Enhance detoxification

24. FINAL INTEGRATED FLOW (CRAM FORMAT)

Normal cell regulation
↓
DNA damage (chemicals/radiation/virus)
↓
Mutation
↓
Oncogene activation + Tumor suppressor loss
↓
Uncontrolled proliferation
↓
Tumor formation
↓
Metastasis
↓
Cancer

25. HIGH-YIELD SUMMARY POINTS

 Cancer = genetic disease of uncontrolled cell growth
 Oncogenes = “accelerators”
 Antioncogenes = “brakes”
 Ras mutation = very common
 p53 loss = critical event
 Phase: initiation → promotion → progression
  Tumor markers = monitoring tools, not definitive diagnosis
 Warburg effect = hallmark metabolic change

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