The Hallmarks of Cancer: Understanding How Normal Cells Turn Rogue
A Discussion on the Six Core Traits That Define Cancer Biology
Hello, friends of Unbiased Science! We hope you enjoyed your Thanksgiving.
In case you missed it, right before the holiday we aired an episode on cancer with Dr. Joe Zundell, all about the basics of cancer biology. It was so good if we do say so ourselves!
The discussion was centered around what scientists have dubbed the “hallmarks of cancer.” What’s that?
In 2000, Douglas Hanahan and Robert Weinberg published a landmark paper, "The Hallmarks of Cancer," which identified six core biological traits that enable tumor growth and survival. These hallmarks provided a foundational framework for understanding cancer biology. In 2011, the model was updated to include emerging hallmarks and enabling characteristics, reflecting advances in cancer research. Additional concepts have since been proposed, further expanding the understanding of cancer's complexity.
In our latest episode, we walk through the six core traits and we have a part 2 in the works that will cover the rest!
Let’s discuss…
What makes cancer, cancer?
Cancer touches the lives of nearly everyone in some way. In the U.S., nearly 1 in 2 men and 1 in 3 women will be diagnosed with cancer at some point in their lives. Globally, cancer accounts for 1 in every 6 deaths, underscoring its far-reaching impact. In 2024 alone, an estimated 2,001,140 new cancer cases are expected in the U.S., with 611,720 lives lost to this disease. Despite its prevalence, cancer isn’t a single illness but rather a diverse group of diseases with unique causes and mechanisms. The most common cancers include breast, prostate, lung, colorectal, and melanoma, along with bladder, kidney, pancreatic, thyroid, liver cancers, leukemia, endometrial cancer, and non-Hodgkin lymphoma. But what is cancer and what makes it so difficult to treat?
What is cancer?
Cancer is unlike other diseases because it isn’t caused by the invasion of an external pathogen. Rather, cancer originates from within us—too much of our own cells. Our bodies are made up of trillions of cells, and over time, these cells can become damaged and die off. Remarkably, we have the ability to replace these damaged cells through a process called cell division, which is vital for maintaining homeostasis and keeping us healthy. Within our cells, there is an intricate system of checks and balances that regulates the process of cell division, ensuring that cells only divide when necessary. However, in cancer, this process goes awry, and cells begin to divide uncontrollably. These unchecked cells can form masses, called tumors, that can grow in nearly any part of the body. Cancer is not a single disease, but a class of diseases caused by a complex combination of genetic and environmental factors, which makes it challenging to study. To help understand the many genetic abnormalities that lead to cancer, scientists have identified common characteristics, known as the hallmarks of cancer. These hallmarks serve as a way to conceptualize the various mechanisms at play across different types of cancer.
Scientists have been studying cells for centuries, and as a result, understand on a very fundamental level how different types of cells behave. This is because healthy cells under normal, or “physiological”, conditions, act according to a very predictable set of rules. However, cancer cells, break almost every single one of these rules in doing so, hijack our bodies. Here is how they do it:
Hallmarks of Cancer Cells
1. Sustaining proliferative signaling: Cancer cells keep dividing and sending signals to grow even when they shouldn’t. They ignore the body’s normal checks on growth.
2. Evading growth suppression: Cancer cells turn off the mechanisms that usually stop cells from continuously growing. They deactivate important genes, such as p53, that prevent tumors.
3. Resisting cell death: Under normal conditions, damaged cells die through a highly regulated process known as apoptosis. Cancer cells resist this process and stay alive even when they are damaged.
4. Becoming Immortal (enabling replicative immortality): Normal cells can only divide a limited number of times (Hayflick Limit). Cancer cells use an enzyme called telomerase to keep dividing indefinitely.
5. Angiogenesis (Creating New Blood Vessels): Tumors need extra nutrients and oxygen to grow. Cancer cells encourage the growth of new blood vessels to feed the tumor.
6. Invasion and Metastasis: Cancer cells spread beyond their original location. They break away from the primary tumor and move to other parts of the body.
These original hallmarks established in 2000 formed the foundation for cancer biology, while the 2011 updates and subsequent concepts highlight the complexity of cancer development. These additions (listed below) emphasize cancer's dynamic interaction with its microenvironment, its ability to evade immune response, and the influence of epigenetics and metabolism. This evolving framework continues to guide research and therapeutic strategies. (As noted, have a part 2 episode in the works that will walk through these updates.) In the meantime, here is a high-level preview:
Expanded Hallmarks and Enabling Characteristics (2011)
Deregulating Cellular Energetics
Cancer cells rewire metabolism (e.g., Warburg effect) to support rapid growth
Genome Instability and Mutation
Increased mutation rates provide genetic diversity for tumor evolution.
Avoiding Immune Destruction
Tumor cells evade immune surveillance by altering surface proteins (e.g., PD-L1 expression).
Tumor-Promoting Inflammation
Chronic inflammation creates a microenvironment that supports cancer growth.
Emerging Concepts in Cancer Biology (Post-2011)
Non-Mutational Epigenetic Reprogramming
Epigenetic changes (e.g., histone modification) deregulate gene expression.
Polymorphic Microbiomes
Microbial communities influence cancer development and therapy responses
Senescence
Cancer cells can enter a state of metabolic activity that promotes tumor growth and immune suppression.
Unlocking Phenotypic Plasticity
Cancer cells lose their defined identities and adopt new functions (e.g., dedifferentiation).
Conclusion
Ultimately, cancer cells are master con artists, deluding and outwitting our bodies’ defense mechanisms by finding new ways of throwing off homeostatic balance. While it may seem overwhelming, research scientists and clinicians are hard at work cracking the code behind the tricky tactics of cancer cells.
By studying the hallmarks of cancer – telltale behaviors that all cancer cells share – we can uncover the playbook that cancer uses to hijack our cells, finding new therapies and treatment strategies along the way. As we continue to learn and innovate, we move closer every day to making the fight against cancer a little more winnable.
Stay curious,
Unbiased Science