Cancer: Characteristics and History

Cancer: A Relentless Division

• Cancer cells are characterized by their uncontrolled division, forming tumors or flooding blood with abnormal cells.
• Normal cells divide for growth and repair, stopping when no longer needed.
• Cancer cells, however, continue dividing indefinitely.
• They also possess the ability to spread to other parts of the body, a process known as metastasis.

A Glimpse into Cancer History

• The earliest known mention of cancer dates back to 1600 BC in the Edwin Smith Papyrus, describing breast cancer.
• Hippocrates described various cancers, using the Greek word "karkinos" (crab) to refer to their appearance.
• Galen, disagreeing with surgery, suggested purgatives for treatment. This approach persisted for a millennium.

Humoral and Lymph Theories

• Hippocrates proposed the humoral theory, suggesting an imbalance of bodily fluids, particularly black bile, could cause cancer.
• The lymph theory followed, attributing cancer to fermenting and degenerating lymph with varying density and acidity/alkalinity.
• John Hunter, a Scottish surgeon, believed tumors grow from lymph constantly released from blood.

The Cellular Nature of Cancer

• Johannes Muller, in 1838, demonstrated cancer's cellular composition, rejecting the lymph theory.
• He suggested cancer cells originated from elements between normal tissues, termed "blastema."
• Rudolph Virchow proposed that all cells, including cancer cells, stem from other cells, suggesting a chronic irritation theory where cancer spreads like a liquid.
• Karl Thiersch, in the 1860s, proved cancer metastasizes by spreading cells, not through a liquid.

Cancer Cell Types

• Cancer cells are categorized based on their origin.
• Carcinoma is the most common, originating in epithelial tissues lining body surfaces.
• Leukemia originates in blood-forming tissues, typically in bone marrow.
• Lymphoma and myeloma are derived from immune system cells.
• Sarcoma arises from connective tissues, including fat, muscle and bone.
• Central nervous system cancers originate in brain and spinal cord cells.
• Mesothelioma originates in the mesothelium, the lining of body cavities.

Six Hallmarks of Malignant Growth

• Self-sufficiency of growth signals: Cancer cells can stimulate their own growth without external signals.
• Insensitivity to growth-inhibitory signals: Cancer cells ignore normal stop signals, continuing to divide.
• Evasion of apoptosis: They can circumvent programmed cell death, preventing their elimination.
• Potential for limitless replication: Cancer cells have the capacity for indefinite division, unlike normal cells.
• Angiogenesis: They induce the formation of new blood vessels to support tumor growth.
• Invasion and metastasis: Cancer cells can invade surrounding tissues and spread to distant sites.

Oncogenes and Proto-oncogenes

• Normal cellular genes that contribute to cancer when altered are called oncogenes.
• Their normal counterparts are referred to as proto-oncogenes.
• Oncogenes are designated by three-letter abbreviations (e.g., myc or ras).
• They are further categorized as "v-" for virus or "c-" for cell, indicating their origin.
• Over 100 oncogenes have been identified.

Apoptosis in Cancer

• Apoptosis is a programmed cell death mechanism.
• Cancer cells evade apoptosis to enable tumor formation.
• Tumor growth depends both on increased proliferation and reduced apoptosis.

Autophagy in Cancer Cells

• Autophagy is a cellular pathway for breaking down proteins and organelles.
• This process delivers cellular materials to lysosomes for degradation.
• It helps maintain a balance between anabolism and catabolism for normal cell growth.
• Autophagy can either eliminate cancer cells or promote tumor development, depending on the context.
• Both stimulating and inhibiting autophagy are considered potential anticancer treatments.

Cancer Invasion: Breaking Through Barriers

• Cancer cells' ability to invade surrounding normal tissues is a key characteristic.
• "In situ cancer" refers to tumors confined to the basement membrane, while "invasive cancer" indicates cells breaching the membrane and penetrating surrounding tissue.
• Invasion involves changes in cell adhesion, motility, and degradation of the extracellular matrix.

Angiogenesis: Building a Blood Supply

• Angiogenesis is the formation of new blood vessels from existing ones.
• This neovascularization is crucial for tumor growth and metastasis.
• Tumors develop an angiogenic phenotype through accumulated genetic alterations and response to local pressures, like hypoxia.
• Many oncogenes and tumor suppressor genes influence angiogenesis.

Metastasis: Spreading the Disease

• Metastasis involves the spread of cancer cells from the primary site to distant sites.
• The process involves several steps:
  • Accessing the circulatory system (blood or lymph).
  • Surviving in the circulation.
  • Lodging in a new organ.
  • Extravasation (exiting the blood vessels).
  • Initiating growth in the new tissue.
  • Establishing vascularization for the new tumor.

Hereditary Cancer

• Hereditary cancers are primarily caused by inherited genetic defects.
• Less than 0.3% of the population carries genetic mutations with a significant impact on cancer risk.
• These mutations cause less than 3-10% of cancers.

Hormones and Cancer

• Some hormones contribute to cancer development by promoting cell proliferation.
• Insulin-like growth factors and their binding proteins play a role in cancer cell growth, differentiation, and apoptosis.
• Hormones are crucial in sex-related cancers (e.g., breast, prostate, ovary), as well as thyroid and bone cancers.

Management of Cancer: Treatment Options

• Surgery: Removal of cancerous tissue from the body.
• Radiation therapy: Using high doses of radiation to kill cancer cells and shrink tumors.
• Chemotherapy: Using drugs to destroy cancer cells.