A new study argues for a revised clonal evolution model of cancer, incorporating genetic and non-genetic factors to improve understanding and treatment.
Like all living organisms, cancer cells are driven by the fundamental need to grow, survive, and reproduce. Although cancer's evolutionary underpinnings have been recognized since the 1950s, clinicians have been slow to apply the lessons of evolution to the fight against this deadly disease, which claimed 9.7 million lives worldwide in 2022 and remains the second-leading cause of death.
In a new study published in the journal Nature Reviews Cancer, Arizona State University researcher Carlo Maley and Lucie Laplane from the University of Paris Pantheon-Sorbonne review the prevailing theory of cancer evolution. The authors identify both practical and theoretical limitations of the clonal model of cancer evolution and propose revisions that could improve the model's accuracy and relevance.
The study suggests that the model could be improved by acknowledging that cancer cells inherit not only genetic mutations but also other traits that allow them to rapidly adapt to their environment — even without genetic alterations. Cancer cells are highly responsive to their surrounding environment, which can promote or suppress their growth. Further, cancer evolution often follows complex dynamics, leading to tangled and unpredictable growth patterns.
Rethinking the Clonal Evolution Model
Cancer biologists have traditionally defined a "clone" as a group of cells descending from a single ancestor cell and sharing the same genetic makeup. But cancer cells mutate so fast that no two cells have the same genetic makeup. The study proposes replacing the concept of a clone with a focus on the cell genealogies that record the history and define the structure of the cells in a tumor.
The value of an effective model lies in its ability to explain how and why cancers evolve and respond to therapy. By refining the clonal evolution model, the study paves the way for more effective cancer therapies that consider the full complexity of cancer cell evolution.
"Evolution is such a powerful idea that when we apply it to the cells in our bodies, it explains how we get cancer and why it is so hard to cure. But, like everything in the real world, it's complicated," Maley says. "We set out to address the complications that people have pointed out and show how they can be integrated into our theory of how cancer works."
Maley is a researcher in the Biodesign Center for Biocomputing, Security and Society, director of the Arizona Cancer Evolution Center, and a professor at ASU's School of Life Sciences.
His collaborator, Lucie Leplane, visited ASU for the research project, thanks to the generous support of the Center for Biology and Society and a grant from the McDonnell Foundation.
Expanding Evolutionary Cancer Theory
The clonal evolution theory of cancer suggests that cancer begins from a single cell that undergoes mutations, enabling it to grow and divide faster than normal cells. As this cell divides, some of its offspring may gain additional mutations that provide even greater advantages in survival and growth. Over time, this process leads to a population of cancer cells that are very diverse but driven by those that are most fit for survival and reproduction in their environment. This theory helps explain why cancers can be so challenging to treat — they continuously evolve, making them adaptable to various therapies and environments.
To address these issues, the researchers explore the limits of the current evolutionary cancer theory. A key challenge is expanding this theory to encompass all the ways cancer evolves, including the inheritance of more than just genes when cells divide and genetic material exchange among cells, as well as developing better methods to identify and track cancer cell variations.
Traditionally, it has been assumed that the DNA of cancer cells largely determines their behavior and progression. This includes how they grow, spread, and respond to treatments. The study challenges this view, highlighting other factors such as the influence of a cell's surrounding environment and epigenetic changes — chemical modifications that alter gene expression without changing the genetic sequence.
Another assumption is that the development of cancer can be traced like a tree, from one main ancestor cell branching out into all the cancer cells found in a tumor. That model implies a neat, predictable pattern of cancer growth. However, the study suggests this is not always the case. Cancer cells can merge (through cell fusion) or acquire traits from other cells. This could make the growth pattern of cancers more complex, resembling more of a network with multiple influences and paths.
Further, while clonal evolution was initially considered a continuous, gradual process, it has been shown to occur during stasis, gradual change, or sudden, punctuated bursts.
Conclusion and Treatment Implications
The clonal evolution model has already brought about a significant shift in how we view cancer, highlighting the disease's profoundly dynamic nature. This shift in perspective has helped discredit the search for a single "magic bullet" treatment and prompted changes in both research and treatment approaches.
Although the clinical impact of evolutionary theory has been limited so far, a range of evolutionary strategies for treatment has shown encouraging results, such as adaptive therapy, which can lead to dramatic improvements in time progression and overall survival.
Understanding the multifaceted nature of cancer evolution is critical for developing more effective treatments. The study suggests that targeting not only genetic mutations but also epigenetic changes and interactions with the surrounding cell environment could improve treatment outcomes.
By refining the clonal evolution model, the study paves the way for more effective cancer therapies that consider the full complexity of cancer cell evolution.
Reference: "The evolutionary theory of cancer: challenges and potential solutions" by Lucie Laplane, and Carlo C. Maley, 10 September 2024, Nature Reviews Cancer.
DOI: 10.1038/s41568-024-00734-2
News
Very low LDL-cholesterol correlates to fewer heart problems after stroke
Brigham and Women's Hospital's TIMI Study Group reports that in patients with prior ischemic stroke, very low achieved LDL-cholesterol correlated with fewer major adverse cardiovascular events and fewer recurrent strokes, without an apparent increase [...]
“Great Unified Microscope” Reveals Hidden Micro and Nano Worlds Inside Living Cells
University of Tokyo researchers have created a powerful new microscope that captures both forward- and back-scattered light at once, letting scientists see everything from large cell structures to tiny nanoscale particles in a single shot. Researchers [...]
Breakthrough Alzheimer’s Drug Has a Hidden Problem
Researchers in Japan found that although the Alzheimer’s drug lecanemab successfully removes amyloid plaques from the brain, it does not restore the brain’s waste-clearing system within the first few months of treatment. The study suggests that [...]
Concerning New Research Reveals Colon Cancer Is Skyrocketing in Adults Under 50
Colorectal cancer is striking younger adults at alarming rates, driven by lifestyle and genetic factors. Colorectal cancer (CRC) develops when abnormal cells grow uncontrollably in the colon or rectum, forming tumors that can eventually [...]
Scientists Discover a Natural, Non-Addictive Way To Block Pain That Could Replace Opioids
Scientists have discovered that the body can naturally dull pain through its own localized “benzodiazepine-like” peptides. A groundbreaking study led by a University of Leeds scientist has unveiled new insights into how the body manages pain, [...]
GLP-1 Drugs Like Ozempic Work, but New Research Reveals a Major Catch
Three new Cochrane reviews find evidence that GLP-1 drugs lead to clinically meaningful weight loss, though industry-funded studies raise concerns. Three new reviews from Cochrane have found that GLP-1 medications can lead to significant [...]
How a Palm-Sized Laser Could Change Medicine and Manufacturing
Researchers have developed an innovative and versatile system designed for a new generation of short-pulse lasers. Lasers that produce extremely short bursts of light are known for their remarkable precision, making them indispensable tools [...]
New nanoparticles stimulate the immune system to attack ovarian tumors
Cancer immunotherapy, which uses drugs that stimulate the body’s immune cells to attack tumors, is a promising approach to treating many types of cancer. However, it doesn’t work well for some tumors, including ovarian [...]
New Drug Kills Cancer 20,000x More Effectively With No Detectable Side Effects
By restructuring a common chemotherapy drug, scientists increased its potency by 20,000 times. In a significant step forward for cancer therapy, researchers at Northwestern University have redesigned the molecular structure of a well-known chemotherapy drug, greatly [...]
Lipid nanoparticles discovered that can deliver mRNA directly into heart muscle cells
Cardiovascular disease continues to be the leading cause of death worldwide. But advances in heart-failure therapeutics have stalled, largely due to the difficulty of delivering treatments at the cellular level. Now, a UC Berkeley-led [...]
The basic mechanisms of visual attention emerged over 500 million years ago, study suggests
The brain does not need its sophisticated cortex to interpret the visual world. A new study published in PLOS Biology demonstrates that a much older structure, the superior colliculus, contains the necessary circuitry to perform the [...]
AI Is Overheating. This New Technology Could Be the Fix
Engineers have developed a passive evaporative cooling membrane that dramatically improves heat removal for electronics and data centers Engineers at the University of California San Diego have created an innovative cooling system designed to greatly enhance [...]
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
Mystery Solved: Scientists Find Cause for Unexplained, Deadly Diseases
A study reveals that a protein called RPA is essential for maintaining chromosome stability by stimulating telomerase. New findings from the University of Wisconsin-Madison suggest that problems with a key protein that helps preserve chromosome stability [...]
Nanotech Blocks Infection and Speed Up Chronic Wound Recovery
A new nanotech-based formulation using quercetin and omega-3 fatty acids shows promise in halting bacterial biofilms and boosting skin cell repair. Scientists have developed a nanotechnology-based treatment to fight bacterial biofilms in wound infections. The [...]
Researchers propose five key questions for effective adoption of AI in clinical practice
While Artificial Intelligence (AI) can be a powerful tool that physicians can use to help diagnose their patients and has great potential to improve accuracy, efficiency and patient safety, it has its drawbacks. It [...]
