FEB 27, 2016 10:55 AM PST

Counter-Intuitive Treatment Kills More Breast Cancer Cells

WRITTEN BY: Xuan Pham
Image credit: Pixabay.com


Survival of the fittest has a generally positive connotation. After all, this evolutionary principle is the driving force behind how our species got to be so advanced. But in terms of cancer, survival of the fittest could mean aggressive cancer cell populations that are especially lethal because they’ve adapted to be resistant to drugs.
 
To improve treatment outcomes, researchers at the Moffitt Cancer Center are experimenting with a new strategy that may seem counter-intuitive. Instead trying to wipe out the entire cancer cell population in one go, the team is attempting to eradicate cancer slowly, steadily, and completely. This new method is termed “adaptive therapy,” and is based on evolutionary principles of adaptation.
 
In standard cancer treatments, doctors administer chemotherapy drugs at the maximum dose a patient can tolerate. This high dose effectively kills chemo-sensitive cancer cells, but it also acts to select for the strongest and most drug-resistant cancer cells. These chemo-resistant cells are among oncologists’ worst nightmare, as they’ve become immune to therapies.
 
“There is a natural tendency to use high-dose therapy based on the assumption that each patient receives maximum benefit by killing as many cancer cells as possible. However, according to evolutionary principals, high-dose therapy is the least likely to be successful in controlling the tumor for any length of time because it intensely selects for resistant cells and allows them to grow rapidly because the treatment has eliminated all of their competitors,” said Robert Gatenby, senior study author and leader of the Cancer Biology & Evolution Program at Moffitt.
 
To circumvent selection of these chemo-resistant cancer cells, researchers at the Moffitt Cancer Center used short bursts of therapy that kills cancerous cells without selective pressure. The strategy, tested first with mathematical models, maintains a steady population of chemo-sensitive cells, which prevent the chemo-resistant cells from taking over.
 
The team demonstrated the logic of this new therapy in mouse models of triple negative and ER+ breast cancer. These mice were separated into three groups and treated with different dosing strategies of paclitaxel. The first group received the maximum standard dose (ST), the second group received an adaptive-therapeutic dose (AT-1) where paclitaxel dose decreased as the tumor shrank, and the third group received a modified adaptive-therapeutic dose (AT-2), in which doses were skipped as the tumor responded.
 
They found that the best outcome were mice treated with the AT-1 therapy, in which they adapted lower paclitaxel doses in response to the tumor shrinking. Mice in this group had sustained tumor remission, while the tumors in the other treatment reverted to growing again after briefly decreasing. AT-1 mice had the longest survival outcomes.
 
“It is hard to get people to think of an alternative approach in which less therapy might actually be more effective over time. We want to try to work with evolution rather than letting evolution be a source of our defeat," explained Gatenby.
 
The adaptive treatment strategy is now being assessed in clinical trial for prostate cancer, a disease also known for high rates of drug-resistance.
 

 
Sources: Science Translational Medicine, Moffitt Cancer Center

About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
DEC 05, 2018
Cardiology
DEC 05, 2018
Top 5 Medical Tests to Predict Heart Disease
  A group of five simple medical tests provides doctors and patients a long-term, wide-range glimpse into a person’s risk of developing heart di...
JUN 18, 2018
Immunology
JUN 18, 2018
Detecting and Diagnosing Rheumatoid Arthritis Before it Begins
Unique gene signatures and tiny changes in the immune system that occur in the earliest stages of rheumatoid arthritis, an autoimmune disease, could soon b...
OCT 16, 2018
Microbiology
OCT 16, 2018
Simple Test Rapidly Diagnoses Antibiotic-resistant Infections
If we get a bacterial infection, doctors use antibiotics to treat it. But sometimes people are infected by pathogens that are resistant to drugs....
OCT 29, 2018
Immunology
OCT 29, 2018
Escape of the Tumor Cell
Tumor cells in breast cancer have proven to evade the immune responses utilizing actin cytoskeleton...
OCT 29, 2018
Immunology
OCT 29, 2018
Immunity for All
A study published in Nature has shed light on the evolution of immune system genes across species with great detail at the single-cell level...
OCT 30, 2018
Drug Discovery
OCT 30, 2018
Re-sensitizing Drug-resistant Human Tumor Cells
Understanding how cancer cells avoid death despite their DNA being damaged will create new strategies to enhance cancer cell killing through chemotherapy t...
Loading Comments...