Oncology
Cancer Cells
The hallmarks of cancer — how normal cells become invasive tumors
Cancer is a disease of dysregulated cell behavior. Hanahan and Weinberg defined eight hallmarks: sustained proliferation, evasion of growth suppressors, resistance to cell death, replicative immortality, induced angiogenesis, invasion and metastasis, reprogrammed metabolism, and immune evasion. Two enabling characteristics: genome instability and tumor-promoting inflammation. A normal cell typically requires 5-7 driver mutations to become malignant. Cancer kills ~10 million people per year worldwide.
- Hallmarks8 capabilities + 2 enabling
- Driver mutations needed~5-7 for full malignancy
- Most common cancersLung, breast, colorectal, prostate
- Key tumor suppressorTP53 ("guardian of the genome")
- Key oncogeneRAS (mutated in 25% of cancers)
- Annual deaths~10 million globally
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Why cancer biology matters
- Targeted therapy. Imatinib for BCR-ABL CML; trastuzumab for HER2 breast cancer.
- Immunotherapy. Checkpoint inhibitors and CAR-T cells revolutionized melanoma, leukemia.
- Screening. Mammogram, colonoscopy, low-dose CT lung, Pap, PSA.
- Genetic testing. BRCA1/2, Lynch syndrome guide prevention and family counseling.
- Liquid biopsy. ctDNA detects minimal residual disease earlier than imaging.
- Vaccines. HPV vaccine prevents cervical/oropharyngeal cancers; hepatitis B prevents HCC.
- Lifestyle. ~40% of cancers are preventable: tobacco, obesity, alcohol, infection, UV.
Common misconceptions
- Cancer is one disease. Hundreds of distinct diseases with different drivers and treatments.
- Sugar feeds cancer. Cancer cells use glucose, but dietary sugar restriction doesn't shrink tumors.
- All tumors metastasize. Benign tumors (lipoma, fibroadenoma) lack invasion machinery.
- Antioxidants prevent cancer. Beta-carotene increased lung cancer in smokers (CARET trial).
- Biopsy spreads cancer. Risk of seeding is rare; benefit of diagnosis is enormous.
- Stage IV is always terminal. Testicular, lymphoma, some lung NSCLC with PD-L1 high are curable.
Frequently asked questions
What are oncogenes versus tumor suppressors?
Oncogenes are mutated proto-oncogenes that drive growth — gain of function. RAS, MYC, HER2, BRAF, EGFR. One mutated allele suffices (dominant). Tumor suppressors restrain growth — loss of function. TP53, RB1, APC, BRCA1/2, PTEN. Knudson two-hit hypothesis: both alleles must be inactivated (recessive at the cellular level).
How does cancer become immortal?
Normal somatic cells have ~50 division limit (Hayflick) due to telomere shortening. Cancer cells reactivate telomerase (~85%) or use ALT (alternative lengthening of telomeres, ~15%) to maintain telomeres indefinitely. Combined with bypass of checkpoints (p53, Rb), they divide without limit. Cell lines like HeLa have proliferated since 1951.
Why do tumors recruit blood vessels?
Beyond ~2 mm, diffusion can't supply oxygen — cells become hypoxic. HIF-1α stabilizes; transcribes VEGF; new vessels sprout (angiogenesis). Tumor vessels are leaky, tortuous, poorly organized. Bevacizumab (anti-VEGF) starves tumors but causes hypertension and bleeding. Tumors switch on glycolysis (Warburg effect) to survive hypoxic regions.
How does metastasis work?
Multi-step. Local invasion (loss of E-cadherin, EMT, MMPs degrade basement membrane). Intravasation into lymph or blood. Survival in circulation (most die from shear, NK cells). Extravasation at distant site. Colonization (most arrest as micrometastases; some grow). Site preference: breast→bone/liver/lung; colon→liver; melanoma→brain. <0.01% of circulating cells form metastases — the rate-limiting step.
What is the role of p53?
"Guardian of the genome." Activated by DNA damage, hypoxia, oncogene stress. Triggers cell-cycle arrest (via p21), DNA repair, or apoptosis (via BAX, PUMA). Mutated in >50% of human cancers. Li-Fraumeni syndrome: germline TP53 mutation; lifetime cancer risk ~90%. Restoring p53 function in tumors causes regression in mouse models.
How do cancer cells evade the immune system?
Express PD-L1 to engage PD-1 on T cells (exhaustion). Secrete TGF-β and IL-10 to recruit Tregs and MDSCs. Lose MHC class I expression. Mutate antigens. Checkpoint inhibitors (pembrolizumab, nivolumab — anti-PD-1; ipilimumab — anti-CTLA-4) block these brakes; durable remissions in melanoma, lung, RCC, MMR-deficient cancers. Honored with 2018 Nobel.
Why is cancer hard to treat?
Tumor heterogeneity — different clones in same tumor; resistant subclones expand under treatment. Drugs select for resistance (EGFR T790M after gefitinib; ABL T315I after imatinib). Sanctuary sites (CNS) limit drug penetration. Toxicity to dividing normal cells (marrow, gut, hair). Combination therapy and circulating tumor DNA monitoring help; cure remains elusive in most metastatic solid tumors.