How targeting metabolism can defeat cancer stem cells

Researchers are the University of Michigan Rogel Cancer are unraveling a crucial thread that explains why cancer so often becomes resistant to treatment. In a breakthrough finding in 2003, Max S. Wicha, M.D., and colleagues discovered that a small number of cells within a tumor - the cancer stem cells - were responsible for fueling the growth and spread of cancer. Kill the stem cells, and you could master the cancer.

But cancer is like a game of whack-a-mole. Strike it down in one place and it pops back up in another.

Now, researchers have found that cancer stem cells exist in more than one state and are very plastic, meaning they can change form, sliding back and forth between a dormant state and a rapidly growing state. This plasticity is responsible for cancer's two key characteristics: multiplying and spreading.

"When we use targeted therapies, they often only work for a certain period of time, and then the cancer becomes resistant. A lot of that resistance is from the cancer stem cells. They change form to evade the targeted therapy," says Wicha, Madeline and Sidney Forbes Professor of Oncology and director of the Forbes Institute for Cancer Discovery at the Rogel Cancer Center.

"This tells us we're going to need multiple stem cell therapies to attack multiple forms of stem cells," he says.

It turns out the cell metabolism controls this change, suggesting a possible way in to attack the stem cells.

Cells get energy through mitochondria, which depends on oxygen, and through sugar, or glucose. Cancer stem cells pull energy both ways. In the dormant state, it uses glucose; in the proliferative state it depends on oxygen.

So researchers attacked the metabolism in both ways. They used a drug currently used to treat arthritis that's known to block mitochondria, and they manipulated glucose to block that path. They tested this in mice with breast cancer and found they were able to knock out the stem cells. Results are published in Cell Metabolism.

"Rather than just try to use toxic chemicals to kill a cell, we use the metabolism of the cell itself to kill the cancer," Wicha says.

Researchers are also understanding that the immune system is regulated by metabolism, suggesting the possibility of combining anti-stem cell therapies with immunotherapies.

Researchers hope to bring this concept to the clinic in the next few years.

Ming Luo, Li Shang, Michael D Brooks, Evelyn Jiagge, Yongyou Zhu, Johanna M Buschhaus, Sarah Conley, Melissa A Fath, April Davis, Elizabeth Gheordunescu, Yongfang Wang, Ramdane Harouaka, Ann Lozier, Daniel Triner, Sean McDermott, Sofia D Merajver, Gary D Luker, Douglas R Spitz, Max S Wicha.
Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling.
Cell Metabolism, Volume 28, Issue 1, 10.1016/j.cmet.2018.06.006.

Most Popular Now

Lilly begins world's first study of a potential CO…

Eli Lilly and Company (NYSE: LLY) announced patients have been dosed in the world's first study of a potential antibody treatment designed to fight COVID-19. This inve...

GSK COVID-19 vaccine development collaboration wit…

GSK's scientific collaboration with Clover Pharmaceuticals to develop an adjuvanted COVID-19 vaccine has entered into human clinical trials. Clover announced the initiati...

Novartis research shows technology talent increasi…

Novartis revealed the healthcare and pharma industry has emerged as a desired career destination for tech talent during the COVID-19 pandemic, in the Powerful Pairing res...

Pfizer and BioNTech announce early positive data f…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced preliminary data from the most advanced of four investigational vaccine candidates from their BNT16...

Sanofi invests to make France its world class cent…

Sanofi detailed plans on how the Company will make significant investments in France to increase its vaccines research and production capacities, and contribute in respon...

Low-cost dexamethasone reduces death by up to one …

In March 2020, the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomised clinical trial to test a range of potential treatments for C...

Novartis resolves legacy litigation matters, final…

Novartis has finalized its previously disclosed agreement with the US Attorney's Office for the Southern District of New York, the New York State Attorney General, and re...

Sanofi and Translate Bio expand collaboration to d…

Sanofi Pasteur, the vaccines global business unit of Sanofi, and Translate Bio (NASDAQ: TBIO), a clinical-stage messenger RNA (mRNA) therapeutics company, have agreed to ...

Bayer supports "The Challenge Initiative…

Today Bayer announced the support of "The Challenge Initiative" ("TCI" hereafter) with a payment of 10 million USD. Hosted at the Johns Hopkins Bloomberg School of Public...

Newer variant of COVID-19-causing virus dominates …

Research out today in the journal Cell shows that a specific change in the SARS-CoV-2 coronavirus virus genome, previously associated with increased viral transmission an...

Mayo finds convalescent plasma safe for diverse pa…

Mayo Clinic researchers and collaborators have found investigational convalescent plasma to be safe following transfusion in a diverse group of 20,000 patients. The findi...

Researchers identify potent antibody cocktail to t…

Researchers at the University of Maryland School of Medicine (UMSOM) evaluated several human antibodies to determine the most potent combination to be mixed in a cocktail...