Cancer Biology

Cancer Biology Overview

Cancer biology is the study of the molecular and cellular basis of cancer, a group of diseases characterized by uncontrolled cell growth and the ability of cells to invade other parts of the body. Unlike normal cells, cancer cells bypass the usual regulatory signals that control cell proliferation and survival, resulting in tumor formation and, potentially, metastasis.

1. Formation of Tumors

A tumor is an abnormal mass of tissue resulting from excessive cell division. Tumor formation begins when a single cell acquires mutations that override normal growth controls, allowing it to divide more rapidly and resist cell death. Tumors can be benign (non-cancerous) or malignant (cancerous). Malignant tumors invade nearby tissues and can spread to distant body sites in a process called metastasis.

• Key Mutations: Tumor formation often involves mutations in oncogenes (promote cell division), tumor suppressor genes (limit cell division), and genes that regulate DNA repair, which collectively drive uncontrolled growth.

2. Loss of Contact Inhibition

In healthy tissues, contact inhibition is a process where cells stop dividing when they touch neighboring cells, helping to maintain proper tissue structure and prevent overgrowth. Cancer cells, however, lose this regulatory control, known as loss of contact inhibition. This allows them to continue dividing and piling up, contributing to tumor formation and progression.

• Mechanism: Contact inhibition loss is often due to mutations in genes like those encoding cadherins (cell adhesion molecules) or pathways involving the Rho and Rac GTPases, which influence cell-to-cell communication and growth.

3. Anchorage-Independent Growth

Normal cells typically require attachment to a solid surface, like the extracellular matrix, to grow and survive, a phenomenon known as anchorage dependence. Cancer cells, however, can grow without attachment, a feature known as anchorage-independent growth. This ability allows cancer cells to survive in suspension, such as when they invade new tissues or circulate in the bloodstream.

• Significance: Anchorage-independent growth is a hallmark of malignant transformation and is often assessed in vitro by the ability of cells to grow in soft agar, a semi-solid medium.

4. Immortality

Normal cells have a finite number of divisions due to a process called replicative senescence. However, cancer cells evade this limit, achieving cellular immortality. This is primarily due to the activation of telomerase, an enzyme that maintains the protective ends of chromosomes called telomeres.

• Telomerase Activity: In most somatic cells, telomerase activity is low or absent, leading to progressive telomere shortening with each division. Cancer cells reactivate telomerase, allowing continuous division by preventing telomere erosion, thus avoiding senescence or apoptosis (programmed cell death).

5. Angiogenesis: Formation of Blood Vessels

Angiogenesis is the process by which new blood vessels form from pre-existing vessels, a crucial step for tumor growth beyond a certain size. For tumors to grow beyond 1-2 mm³, they need nutrients and oxygen, which blood vessels supply. Cancer cells release signals (e.g., VEGF - Vascular Endothelial Growth Factor) that stimulate angiogenesis.

• Tumor-Induced Angiogenesis: Cancer cells secrete pro-angiogenic factors and downregulate anti-angiogenic factors to promote the formation of new blood vessels, supporting sustained growth and providing routes for metastasis.

6. Telomerase Activity in Cancer Cells

Telomerase is an enzyme that extends the length of telomeres, the repetitive DNA sequences at the ends of chromosomes that protect genetic information during replication. In most adult cells, telomerase is inactive, causing telomere shortening and eventual cell death. Cancer cells, however, reactivate telomerase to maintain telomere length, achieving cellular immortality.

• Mechanism: Reactivation of telomerase enables cancer cells to avoid replicative senescence, a critical step in the "immortalization" of cancer cells.

Summary of Cancer Biology Hallmarks

• Tumor Formation: Uncontrolled cell division leading to mass formation.
• Loss of Contact Inhibition: Cells continue to grow even when they touch each other.
• Anchorage-Independent Growth: Cells grow without the need to attach to a surface.
• Immortality: Cancer cells escape replicative limits by reactivating telomerase.
• Angiogenesis: Tumors induce new blood vessel formation to support growth.

These mechanisms allow cancer cells to grow uncontrollably, evade cell death, and ultimately metastasize, contributing to cancer progression and making cancer a complex and challenging disease to treat. 

Key Concepts in Cancer Biology

1. Tumor Formation and Growth

   • Cancer begins when cells acquire mutations that allow them to bypass normal growth controls, divide excessively, and resist cell death.
   • Tumors can be benign (non-cancerous) or malignant (cancerous). While benign tumors remain localized, malignant tumors invade nearby tissues and may metastasize to distant body sites.
   • Key Mutations: Tumor formation is driven by mutations in oncogenes (which promote cell division), tumor suppressor genes (which inhibit cell division), and genes regulating DNA repair mechanisms.

2. Hallmarks of Cancer These hallmarks, as defined by researchers Hanahan and Weinberg, represent the biological capabilities that allow cancer cells to thrive:

   • Sustained Proliferative Signaling: Cancer cells continuously signal to divide, often through mutations that activate growth pathways.
   • Evading Growth Suppressors: They disable tumor suppressor pathways, like the p53 and Rb pathways, that normally restrain growth.
   • Resisting Cell Death (Apoptosis): Cancer cells develop ways to avoid apoptosis, even when severely damaged.
   • Replicative Immortality: Cancer cells maintain telomeres, enabling them to divide indefinitely.
   • Angiogenesis: Cancer cells stimulate the formation of new blood vessels to support their growth by supplying nutrients and oxygen.
   • Invasion and Metastasis: Cancer cells invade surrounding tissues and spread to other parts of the body.

3. Loss of Contact Inhibition

   • Normally, cells stop dividing when they contact neighboring cells in a process called contact inhibition. Cancer cells lose this regulatory control, allowing them to continue dividing and forming multilayered masses.
   • Mechanism: Mutations often alter cell adhesion proteins or disrupt cell signaling pathways, enabling cells to disregard spatial growth constraints.

4. Anchorage-Independent Growth

   • Normal cells typically require attachment to a solid surface, like the extracellular matrix, to grow and survive. Cancer cells gain the ability to grow in suspension, a characteristic known as anchorage-independent growth.
   • Significance: This ability allows cancer cells to survive as they invade new tissues and circulate in the bloodstream, a crucial step in metastasis.

5. Cellular Immortality and Telomerase Activity

   • Most cells can only divide a limited number of times before they undergo replicative senescence. Cancer cells avoid this limit by reactivating telomerase, an enzyme that maintains telomeres, the protective DNA caps at chromosome ends.
   • Mechanism: In normal cells, telomere shortening limits cellular lifespan. However, cancer cells increase telomerase activity, extending telomeres and enabling continuous division.

6. Angiogenesis: Formation of New Blood Vessels

   • Tumors need a blood supply to receive nutrients and oxygen for growth beyond a certain size. Cancer cells release signaling molecules like VEGF (Vascular Endothelial Growth Factor) to stimulate angiogenesis, the formation of new blood vessels from pre-existing ones.
   • Mechanism: The new vessels provide sustenance and also create a pathway for cancer cells to enter the bloodstream and metastasize.

7. Metastasis

   • Metastasis is the spread of cancer from the primary tumor site to distant organs. This complex process involves cancer cells detaching from the primary tumor, entering the bloodstream or lymphatic system, surviving in circulation, and colonizing new tissues.
   • Steps of Metastasis:
     1. Local invasion
     2. Intravasation (entry into blood/lymph vessels)
     3. Survival in circulation
     4. Extravasation (exit from vessels into new tissue)
     5. Colonization (growth at the secondary site)