The Hallmarks of Cancer

Diagram illustrating the hallmarks of cancer.

The concept of "The Hallmarks of Cancer" refers to the distinct and complementary capabilities that enable tumor growth and metastatic dissemination. This framework was first proposed by Douglas Hanahan and Robert Weinberg in their seminal paper published in 2000, and it has since become a foundational concept in cancer biology.

The Original Hallmarks

The original six hallmarks of cancer, as proposed by Hanahan and Weinberg, include:

1. Sustaining Proliferative Signaling

Cancer cells have the ability to sustain chronic proliferation. They achieve this by producing growth factors themselves, stimulating normal cells within the tumor-associated stroma to supply growth factors, or by increasing the number of receptors on their surface.

Signal transduction pathways are often altered in cancer cells.

2. Evading Growth Suppressors

Tumor cells can evade growth suppressors that normally regulate cell proliferation. This is often achieved through mutations in tumor suppressor genes such as TP53 and RB1.

3. Resisting Cell Death

Cancer cells can resist programmed cell death, or apoptosis. This resistance is often due to mutations in genes that regulate apoptosis, such as BCL-2 and BAX.

4. Enabling Replicative Immortality

Normal cells have a limited number of divisions before they enter senescence. Cancer cells, however, can maintain their telomeres and thus achieve replicative immortality, often through the activation of telomerase.

5. Inducing Angiogenesis

To sustain their growth, tumors must develop their own blood supply through the process of angiogenesis. This is often mediated by factors such as VEGF (vascular endothelial growth factor).

6. Activating Invasion and Metastasis

Cancer cells can invade surrounding tissues and spread to distant sites in the body, a process known as metastasis. This involves changes in cell adhesion molecules and the extracellular matrix.

Emerging Hallmarks and Enabling Characteristics

In 2011, Hanahan and Weinberg expanded the original framework to include two emerging hallmarks and two enabling characteristics:

Emerging Hallmarks

• Deregulating Cellular Energetics: Cancer cells often exhibit altered metabolism, such as increased glucose uptake and fermentation of glucose to lactate, even in the presence of oxygen (the Warburg effect).
• Avoiding Immune Destruction: Tumors can evade the immune system through various mechanisms, including the expression of immune checkpoint proteins like PD-L1.

Enabling Characteristics

• Genome Instability and Mutation: Cancer cells exhibit increased mutation rates, which can lead to genetic diversity within tumors and contribute to cancer progression.
• Tumor-Promoting Inflammation: Chronic inflammation in the tumor microenvironment can promote cancer development and progression.

Related Pages

• Cancer
• Oncogene
• Tumor suppressor gene
• Metastasis
• Apoptosis

Melanoma cells infiltrating the brain, illustrating the invasive nature of cancer.

Conclusion

The hallmarks of cancer provide a comprehensive framework for understanding the complex biology of cancer. This framework continues to evolve as new discoveries are made, offering insights into potential therapeutic targets and strategies for cancer treatment.