Pancreatic cancer is known for its aggressive behavior and is often diagnosed at an advanced stage, contributing to its high mortality rate. In the United States, it accounts for about 3% of all cancers but causes approximately 7% of cancer-related deaths. The five-year relative survival rate has historically been low, though recent data indicates a slight increase to around 12-13.5%.
The development of pancreatic cancer is a complex process involving interactions between different cellular systems. Research is focused on how a cell’s ability to change its behavior, combined with its communication with its surroundings, directs tumor formation. This collaboration is a focal point for identifying new approaches to this disease.
What Is Epigenetic Plasticity?
Epigenetic plasticity is a cell’s ability to alter its gene expression and function without changing the DNA sequence. Think of DNA as a cookbook; epigenetics acts like sticky notes and highlighters that mark which recipes to follow, ignore, or use frequently. These marks don’t rewrite the recipes but direct how the cookbook is used.
This plasticity is the cell’s capacity to adapt its identity in response to epigenetic instructions, which come as chemical tags on DNA or its associated proteins. One mechanism is DNA methylation, where methyl groups are added to DNA, often acting as a switch to turn genes off. Another is histone modification, where proteins that package DNA are altered to make genes more or less accessible for activation.
These epigenetic marks are dynamic and can be influenced by factors like environmental signals, diet, and aging. This flexibility allows cells to respond to their environment and perform specialized functions. It provides a layer of control over the genome, enabling cells to have different behaviors despite sharing the same genetic blueprint.
Cell Communication in the Tumor Environment
A tumor is not just a mass of cancer cells; it exists within a complex neighborhood known as the tumor microenvironment (TME). The TME is an ecosystem of different cell types in constant communication. The cancer cells are surrounded by a diverse cast of other cells.
These neighbors include:
- Stromal cells, such as fibroblasts, which provide structural support to tissues.
- Immune cells, like macrophages and lymphocytes, which fight invaders and remove damaged cells.
- Blood vessels that supply nutrients.
- The extracellular matrix, a network of proteins providing structural scaffolding.
Communication between these cell types involves a network of messages. Cells release signaling molecules, like growth factors and cytokines, that act as chemical messages. These signals travel to nearby cells and bind to surface receptors, triggering an internal response that can influence cell growth, survival, and movement.
How Epigenetics and Cell Interactions Cooperate
Epigenetic plasticity and cellular communication are intertwined and cooperate to drive tumor development. Signals exchanged within the tumor microenvironment can directly cause epigenetic changes in cancer cells, altering their behavior and fueling the disease’s progression.
An example of this cooperation is the interaction between stromal and cancer cells. A fibroblast in the TME can release a signaling molecule that reaches a nearby cancer cell. This molecule binds to a receptor and initiates an internal cascade, leading to the activation of enzymes that add or remove epigenetic marks at specific gene locations.
For instance, a signal might trigger an enzyme to remove a methyl group from a gene that promotes cell division, switching that gene “on.” This epigenetic change, prompted by the external message, allows the cancer cell to grow more aggressively. The process can become a feedback loop, as the altered cancer cell can send its own signals to influence fibroblasts, creating a more supportive environment.
This collaboration is not a one-way street, as cancer cells actively remodel their surroundings. They send signals that corrupt neighboring cells, such as “educating” immune cells to ignore or protect the tumor. This back-and-forth communication, mediated by epigenetic changes, allows the tumor to function as a cohesive unit.
The Pathway from Cooperation to Cancer Growth
The synergy between cellular interactions and epigenetic changes translates into the aggressive characteristics of pancreatic cancer. The feedback loops between cancer cells and their microenvironment lead to destructive outcomes. This cooperation drives the disease’s most aggressive behaviors.
As the TME becomes more corrupted, it provides signals that promote uncontrolled growth. These signals trigger epigenetic modifications that lock cancer cells into a state of proliferation. Genes that act as brakes on cell division are silenced by epigenetic marks, while growth-promoting genes are switched on, allowing the tumor to expand.
This interplay also enables cancer cells to acquire new abilities. Epigenetic reprogramming can activate genes that allow cells to break away from the primary tumor and invade surrounding tissues, a process known as metastasis. Supportive stromal cells can create pathways for invasion, while cancer cells gain migratory tools through epigenetic adaptation, allowing the cancer to spread.
New Avenues for Pancreatic Cancer Treatment
Understanding the partnership between epigenetic regulation and cell communication opens new strategies for treating pancreatic cancer. Researchers can devise therapies aimed at disrupting this cooperation. Instead of targeting only cancer cells, treatments can be designed to dismantle the supportive network and reprogram the instructions driving the disease.
One approach involves drugs that target the epigenetic machinery. These therapies, called epigenetic inhibitors, are designed to correct faulty epigenetic marks in cancer cells. For example, demethylating agents can remove methyl groups that are silencing tumor-suppressor genes, reactivating the cell’s natural defenses and pushing them toward a less aggressive state.
A complementary strategy focuses on blocking communication within the TME. This involves therapies that intercept signaling molecules sent between cancer cells and their neighbors. By blocking a growth factor or its receptor, these treatments cut off supportive messages that cancer cells rely on, isolating them and making them more vulnerable.