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Chapter 12: Cancer Biology

Overview of Cancer

• Leading Causes of Death in the U.S. (2018):

  • Total deaths: 2,839,205

  • Major causes:

    • Heart Disease

    • Cancer (malignant neoplasms)

    • Preventable injury

    • Chronic lower respiratory diseases

    • Stroke

    • Alzheimer's Disease

    • Diabetes Mellitus

    • Influenza and pneumonia

    • Nephritis

    • Suicide

What is Cancer?

• Derived from the Greek word "karkinoma" (meaning crab), referring to its malignant properties.

• Characteristics of Cancer:

  • Abnormal growth due to uncontrolled cell proliferation.

  • Serves no physiological function.

  • Also referred to as neoplasms (new growth).

Classification and Nomenclature

• Tumor Naming:

  • Most tumors have the suffix -oma (e.g., lipoma).

  • Exceptions: leukemias.

• Types of Tumors:

  • Benign tumors - Non-cancerous

  • Malignant tumors - Cancerous:

    • Carcinomas: originate from epithelial tissue

    • Adenomas: glandular tissue

    • Sarcomas: connective tissue

    • Lymphomas: originating from lymphatic tissue

    • Leukemias: blood-forming tissue

  • Carcinoma in situ (CIS): preinvasive stage of cancer.

Benign vs. Malignant Tumors

Biology of Cancer Cells

• Disease of Aging:

  • Cancer arises from clonal proliferation and expansion.

  • Accumulation of mutations leads to increased growth rates or decreased apoptosis.

• Key Concepts:

  • Sustaining proliferative signaling.

  • Deregulating cellular energetics.

  • Avoiding immune destruction.

  • Evading growth suppressors.

  • Enabling replicative immortality.

  • Tumor-promoting inflammation.

  • Resisting cell death.

  • Inducing angiogenesis.

  • Activating invasion and metastasis.

  • Genomic instability (mutator phenotype).

Genomic Hallmarks of Cancer

• Types of Genetic Changes:

  • Gene Amplification

    Chromosome Translocations (e.g., Philadelphia chromosome)

  • Clonal Proliferation leading to mutations

• Driving Mutations:

  • Activation of proto-oncogenes.

  • Inactivation of tumor-suppressor genes.

  • Overexpression of cellular products promoting proliferation or preventing apoptosis.

Cancer Resistance Mechanisms

• Resistance to Destruction:

  • Involvement of chronic inflammation in cancer development.

  • Evading Immune Destruction:

    • Tumor-associated antigens lead to immune responses.

    • Tumor cells may develop mechanisms to evade T cell recognition and activation.

• Inflammatory Factors:

  • Chronic inflammation can stimulate cell proliferation (e.g., ulcerative colitis associated with colon cancer).

Invasion and Metastasis

• Mechanisms of Invasion:

  • Epithelial-mesenchymal transition (EMT) increases cancer cell migration.

  • Cancer cells secrete proteases to break down the extracellular matrix.

• Metastasis involves complex processes:

  • Cells survive in new environments, travel through circulation, and establish at new sites.

Clinical Manifestations of Cancer

• Paraneoplastic Syndromes:

  • Symptoms triggered by cancer but not directly caused by the tumor.

• Cachexia:

  • A severe form of malnutrition commonly associated with cancer. Observed symptoms: anorexia, weight loss, altered metabolism.

Diagnosis and Staging of Cancer

• Stages:

  • Stage 1: Cancer confined to the organ of origin.

  • Stage 2: Locally invasive.

  • Stage 3: Spread to regional structures.

  • Stage 4: Distant metastasis.

• Staging Systems:

  • TNM Classification:

    • T (Tumor size and local extent)

    • N (Nodes involvement)

    • M (Metastases presence)

Tumor Markers

• Function: Used for screening, diagnosis, and monitoring cancer progression. Common examples include:

  • Alpha-fetoprotein (AFP) - liver and germ cell tumors

  • Prostate-specific antigen (PSA) - prostate tumors

Treatment of Cancer

• Classical Treatments:

  • Surgery: Can be palliative or preventive.

  • Radiation Therapy: Focused beams, brachytherapy (radioactive seeds).

  • Chemotherapy: Variable side effects, used as induction, adjuvant, or neoadjuvant therapy.

• New Treatments:

  • Immunotherapy: Both active and passive immunization strategies.

  • Gene Therapy: Targeting cancer on a genetic level using engineered CARs.