Applied Pathophysiology: Cancer Mechanisms

Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease

• This lecture series covers applied pathophysiology, focusing on the mechanisms of disease.
• It specifically examines altered cellular proliferation and differentiation, particularly the impact of cancer on the cell.

Cancer Statistics (Australia 2017)

• Prostate cancer was the most commonly diagnosed cancer in males (16,665 cases).
• Breast cancer was the most commonly diagnosed cancer in females (17,586 cases)
• Colorectal cancer was the third most common in both genders.
• Lung cancer is a leading cause of death in both genders
• A range of other cancers are also prominently represented in the statistics.

Cancer: Definition and Characteristics

• Cancer is characterized by uncontrolled cell proliferation.
• It's derived from Greek words "crab" (carcinos), and "tumor" (carcinoma).
• Hippocrates and Celsus recognized early forms of cancer characterized as "finger-like projections"
• Also referred to as a neoplasm, meaning "new growth".
• Cancer can be a chronic condition with periods of remission and relapse.
• Not all tumours are cancerous.

Cell Proliferation

• Cell proliferation is the process of increasing cell numbers.
• In normal tissue, this process is regulated.
• Human cells are categorized as somatic cells and gametes.
• Somatic cells operate via mitosis, while gametes use meiosis.
• Cell types within the body are divided into three large groups.

Cell Differentiation

• Cell differentiation is the process of proliferating cells becoming progressively specialized.
• Results in fully differentiated adult cells with specific structures, functions, and life expectancies.
• An example is red blood cells (RBCs), which are terminally differentiated, concave, carry oxygen and have a lifespan of 120 days.

Stem Cells

• Stem cells are highly undifferentiated reserve cells with the potential to divide into progenitors.
• Stem cells have self-renewal and potency through stem cell division (stem cell + progenitor)

Normal vs. Cancer Cells

• Normal cells grow, divide, differentiate, and are in communication with neighboring cells. They respond to the environment and die as needed.
• Cancer cells exhibit abnormal growth, no longer respond to regulatory mechanisms such as contact inhibition/recognition, reproduce uncontrollably, and may grow outside the original tissue of origin

Carcinogenesis

• Definition: The origin and development of cancerous neoplasms.
• Neoplasms are irreversible deviant cellular developments.
• Factors that initiate cancer and promote its spread are considered carcinogens.
• Cancer is a highly invasive and destructive neoplasm.

Carcinogens: Identification and Agents

• Carcinogens can be identified via: Epidemiology studies, experimental research, and cell and molecular pathology.
• They can interfere with crucial molecular pathways (initiate, promote, or facilitate tumour creation or growth).

Genetics Basis of Cancer

• Cancer arises from genetic mutations and usually requires multiple mutations.
• Mutations may occur spontaneously.
• Mutations may be acquired after conception or inherited.
• Exposure to environmental mutagens or inherited predisposition can increase cancer risk.

Role of Genes in Cancer

• Mutator genes: Involved in DNA repair.
• Oncogenes: Genes that promote uncontrolled cell proliferation.
• Tumor suppressor genes: Genes that restrict uncontrolled growth.

Telomeres and Cancer

• Telomeres are protective caps on chromosomes, shortening with each cell division.
• Cancer cells become "immortal" due to telomere repair mechanisms.

Carcinogenesis: Initiation, Promotion, and Progression

• Initiation: Initial mutations in a cell caused by a carcinogen.
• Promotion: Expansion and continuous mutation of the initiated cell, a process that often requires ongoing exposure to a promoting factor.
• Progression: Cancerous growth becomes independent of the promoter; cells grow autonomously, with unrestricted growth, division, and potentially death (apoptosis).

Summary of Initiator-Promoter-Progression Theory

• The initiation of cancer depends on a specific event and the process needs to happen in a sustained way for cancer to develop.
• Initiating exposure triggers irreversible changes.
• Exposure needs to continue for the promoted stage to occur.