What are the Hallmarks of Cancer?
The hallmarks of cancer are a set of characteristics that distinguish cancer cells from normal cells. These hallmarks provide a framework for understanding the complexities of cancer biology. They were first described by Douglas Hanahan and Robert Weinberg in their seminal papers. The hallmarks include sustained proliferative signaling, evasion of growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Additional emerging hallmarks include deregulating cellular energetics and avoiding immune destruction.
Sustained Proliferative Signaling
Cancer cells can continuously signal themselves to proliferate. This is often achieved by mutations in genes encoding for growth factors, growth factor receptors, or downstream signaling molecules. For instance, mutations in the
EGFR gene can lead to constant activation of growth signals.
Evasion of Growth Suppressors
Normal cells have mechanisms to prevent uncontrolled growth. These mechanisms include tumor suppressor genes like
TP53 and
RB1. Cancer cells often harbor mutations that disable these suppressor pathways, allowing for unregulated growth.
Resisting Cell Death
Apoptosis is a programmed cell death mechanism critical for eliminating damaged cells. Cancer cells evade apoptosis by altering pro-apoptotic and anti-apoptotic proteins. Mutations in genes like
BCL-2 help cancer cells avoid this fate.
Enabling Replicative Immortality
Normal cells have a limited number of divisions, known as the Hayflick limit, after which they become senescent. Cancer cells bypass this limit by maintaining the length of their telomeres through the activation of
telomerase or alternative lengthening of telomeres (ALT) mechanisms.
Inducing Angiogenesis
For tumors to grow beyond a certain size, they require a blood supply to deliver oxygen and nutrients. Cancer cells induce the formation of new blood vessels, a process known as
angiogenesis, often by overexpressing pro-angiogenic factors like
VEGF.
Activating Invasion and Metastasis
The ability to spread from the original tumor site to distant organs is a defining feature of cancer. This involves changes in cell adhesion molecules, such as E-cadherin, and the activation of enzymes that degrade the extracellular matrix, allowing cancer cells to invade and establish secondary tumors.Deregulating Cellular Energetics
Cancer cells often alter their metabolism to support rapid growth and survival in the tumor microenvironment. This includes a preference for glycolysis over oxidative phosphorylation, even in the presence of sufficient oxygen, known as the
Warburg effect.
Avoiding Immune Destruction
The immune system is capable of recognizing and destroying cancer cells. However, cancer cells develop strategies to evade immune detection and destruction. This includes the expression of immune checkpoint proteins like
PD-L1 and the recruitment of immunosuppressive cells to the tumor microenvironment.
Conclusion
Understanding the hallmarks of cancer provides critical insights into the mechanisms that drive cancer progression and highlights potential therapeutic targets. Advances in cancer research continue to refine and expand upon these hallmarks, paving the way for more effective treatments.
