Biology of Cancer Flashcards

Cancer Biology

Definition

• Diseases with uncontrolled abnormal cell division and tissue invasion.
• Neoplasm: new growth, also referred to as a tumor.

Benign vs. Malignant Tumors

• Benign:
  • Slow growth, encapsulated, not invasive, well-differentiated, low mitotic index, no metastasis.
• Malignant:
  • Rapid growth, not encapsulated, invasive, poorly differentiated, high mitotic index, can metastasize.

Tumor Classification

• Benign:
  • Slow growth, distinct borders, no invasion.
  • Treatment: surgical removal if compression occurs.
• Malignant:
  • Quick growth, irregular borders, invasion, metastasis.
  • Treatment: surgery, radiotherapy, chemotherapy, immunotherapy, or combinations.

Tumor Naming

• Benign: named by tissue of origin (e.g., lipoma, leiomyoma, meningioma).
• Malignant: named by cell type of origin (e.g., carcinoma, adenocarcinoma, sarcoma, lymphoma, leukemia).

Carcinoma in Situ

• Preinvasive epithelial tumors that have not invaded the basement membrane.
• Outcomes: stable, progress to invasive cancer, or regress.

Biology of Cancer Cells

• Cancer is complex; tumors are heterogeneous.
• Stages: tumor initiation, promotion, progression.
• Multiple driver mutations are required for cancer development.
• Clonal proliferation: advantageous mutations leading to increased growth.

Hallmarks of Cancer

• Genomic Alterations:
  • Sustained proliferative signaling.
  • Evading growth suppression.
  • Genomic instability.
  • Replicative immortality.
• Secondary Genomic Changes:
  • Angiogenesis.
  • Reprogramming energy metabolism.
• Tumor Resistance:
  • Resistance to apoptosis.
  • Tumor-promoting inflammation.
  • Avoiding immune destruction.
• Culmination:
  • Activating invasion and metastasis.

Sustained Proliferative Signaling

• Uncontrolled cell proliferation.
• Proto-oncogenes: direct normal proliferation.
• Oncogenes: mutated proto-oncogenes causing uncontrolled growth.
• Autocrine stimulation: cancer cells secrete their own growth factors.
• Oncogene activation: point mutations, translocations, gene amplification.

Evading Growth Suppressors

• Tumor-suppressor genes (anti-oncogenes):
  • Regulate cell cycle, inhibit proliferation, prevent mutations.
• Inactivation of tumor-suppressor genes:
  • Unregulated growth (e.g., retinoblastoma (RB) gene, tumor protein p53 (TP53)).
• Two mutations needed for inactivation; germ-cell mutations can transmit cancer-causing genes.

Genomic Instability

• Increased mutation tendency.
• Caretaker genes: repair damaged DNA; mutations increase instability.
• Chromosome instability: loss of heterozygosity and chromosome amplification.

Replicative Immortality

• Normal cells have limited divisions.
• Telomeres:
  • Protective caps maintained by telomerase (active in germ and stem cells).
  • Shorten with each division, leading to cell death.
• Cancer cells:
  • Activate telomerase to restore telomeres, allowing unlimited division.

Angiogenesis

• Growth of new blood vessels essential for tumor growth and spread.
• Cancerous tumors secrete angiogenic factors (VEGF) and suppress inhibitors.

Reprogramming Energy Metabolism

• Warburg effect: aerobic glycolysis.
• Oncogenes drive metabolic reprogramming for proliferation and survival.

Resisting Apoptotic Cell Death

• Apoptosis: programmed cell death.
• Defects in apoptotic pathways provide resistance to cell death.

Tumor-Promoting Inflammation

• Chronic inflammation can promote cancer.
• Tumor-associated macrophages (TAMs) promote tumor survival and spread.

Evading Immune Destruction

• Normal immune system protects against cancer.
• Tumor-associated antigens.
• Immune surveillance hypothesis.
• Tumor-infiltrating lymphocytes.

Activating Invasion and Metastasis

• Invasion: local spread.
• Metastasis: spread to distant sites.
• Epithelial-mesenchymal transition (EMT).

Clinical Manifestations

• Paraneoplastic syndromes: Symptom complexes triggered by cancer.
• Cachexia: Multiorgan energy wasting syndrome.

Cancer Staging

• Microscopic analysis based on metastasis.
  • Stage I: No metastasis.
  • Stage II: Local invasion.
  • Stage III: Spread to regional structures.
  • Stage IV: Distant metastasis.
• TNM system (Tumor, Node, Metastasis).

Tumor Markers

• Biochemical markers found in tumor cells, blood, CSF, or urine.
• Used for screening, diagnosis, and monitoring.

Classification of Tumors

• Based on immunohistochemical and genetic analysis.
• Personalized medicine based on tumor characteristics for improved treatment.

Cancer Treatment

• Classic: surgery, chemotherapy, radiation therapy.
• Rapidly evolving immunotherapy.
• Surgery: prevention, diagnosis, staging, palliative.
• Radiation: damage cancer cell DNA.
• Chemotherapy: target vulnerabilities; can harm rapidly dividing non-cancerous cells.
• Immunotherapy: vaccines.
• Targeted disruption: specific, less toxic.