Unraveling A Journey with Yale's Jeffrey Townsend
Cancer's Evolutionary Mysteries Part 1
Written by Lina Shoman
Meet Townsend, a Cancer Evolution Detective
Jeffrey Townsend, Elihu Professor of Biostatistics at Yale University, stands at a cross of biology, statistics, and medicine. As a Professor of Ecology and Evolutionary Biology, his multifunctional approach gives him a unique perspective on cancer research. Rather than focusing only on the disease, Townsend explores cancer through evolution, studying how cancer cells adapt, change, and survive.
Because of these evolutionary principles for understanding cancer's progression, Townsend’s work offers new insights into how cancer develops and spreads. His research challenges traditional cancer treatment methods, focusing on how cancer cells evolve over time, resist treatment, and the environmental factors that influence tumor behavior.
The Birth of Cancer: Cell Mutations
The body functions through a network of cells, each performing specific tasks to maintain homeostasis or internal balance. But sometimes, small mutations in a cell's DNA can build up. Some of these mutations come from natural errors in the cell division process, while others are caused by external factors like UV radiation or smoking.
“These cancer-causing mutations occur in your somatic DNA, not the DNA you pass on to your children,” Townsend explains. Most mutations are either harmless or cause a cell to malfunction and die. On rare occasions though, a mutation allows a cell to grow faster or resist death, giving it a dangerous advantage on causing cancer. A cell with such a mutation can multiply uncontrollably, eventually leading to the formation of a tumor. This means that what was once a healthy, functioning tissue becomes a spawning ground for cancer cells.
How Normal Cells Turn Rogue
The process of turning a normal cell into a cancer cell is like a rolling dice—a specific combination is needed for cancer to form, like statistics. These changes can happen in many ways: replication errors during cell division, exposure to harmful chemicals, or even lifestyle choices like smoking or drinking.
Townsend notes that while many mutations are harmless, “the process of mutation sometimes causes changes that, instead of damaging the cell, make it grow faster rather than slower.” In these rare cases, the cell gains a growth advantage and can start to multiply unchecked.
However, cancer doesn’t usually result from just one mutation. It often takes multiple changes over time for a cell to fully transform. As these mutations pile up, the cell becomes better at surviving, dividing, and even resisting the body’s defense mechanisms.
The Stages of Cancer Evolution
Once a rogue cell has enough mutations, it can form a tumor which is a mass of cells growing uncontrollably. The early stages of tumor growth may go unnoticed, but as the tumor expands, it starts to interfere with normal tissue function. This is when cancer becomes more dangerous.
A key factor in cancer’s adaptability is its ability to evolve, like species in nature, or bacteria resistance! Townsend and his team study how cancer cells develop resistance to treatments like chemotherapy. By applying evolutionary principles, they try to predict how cancer will change in response to therapies and how new treatment strategies can stay one step ahead of the disease.
Tumor genesis isn’t a linear process—it involves multiple stages:
Initiation: The first mutation occurs, giving the cell a slight edge in growth.
Promotion: Cells with this mutation begin to multiply, expanding the initiated population.
Progression: Additional mutations accumulate, allowing these cells to become malignant, evade immune detection, and spread further.
These changes within the tumor are not uniform; each cancer cell within the tumor may carry a slightly different set of mutations. This phenomenon, known as tumor heterogeneity, is part of what makes cancer so difficult to treat. The cells can evolve rapidly, leading to treatment resistance. Townsend’s work is focused on this point—understanding how cancer evolves to survive.
Demystifying Metastasis
Metastasis—the spread of cancer cells from the primary tumor to other parts of the body—is the most dangerous phase of cancer progression. This process begins when cancer cells break away from the primary tumor, enter the bloodstream or lymphatic system, and establish new tumors in distant organs.
“When things become metastatic, the cells no longer remain in place and move somewhere else,” Townsend explains. These metastatic cells are notoriously resilient, often developing resistance to treatments and thriving in environments where they don’t belong.
Metastasis follows a complex cascade:
Local Invasion: Cancer cells first break through the basement membrane and begin to invade nearby tissues.
Intravasation: The cancer cells enter the blood or lymphatic vessels, allowing them to travel through the body.
Circulation: Once in the bloodstream, cancer cells face numerous challenges, including immune cells that attempt to eliminate them.
Extravasation: Some cancer cells manage to exit the bloodstream and lodge in a new tissue or organ.
Colonization: Once settled in a new location, the cancer cells must adapt to their new environment, forming micrometastases that eventually grow into full-blown metastatic tumors.
Townsend’s research is focused on understanding the genetic mutations that allow cancer cells to survive this journey.
“It’s hard to understand because all these systems in the body are supposed to allow only the right kind of cells to grow in the right kind of environment.”
By finding the mutations that support metastatic behavior, Townsend hopes to develop therapies that can target cancer cells before they spread, or block their ability to thrive in new environments!
