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

US FDA grants Lynparza Orphan Drug Designation for…

AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) announced that they were granted orphan drug designation (ODD) by ...

Eating leafy greens could help prevent macular deg…

A new study has shown that eating vegetable nitrates, found mainly in green leafy vegetables and beetroot, could help reduce your risk of developing early-stage age-relat...

FDA approves new drug to treat influenza

The U.S. Food and Drug Administration approved Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older...

Alcon to develop SMART Suite digital health platfo…

Alcon, the global leader in eye care and a division of Novartis, today announced plans to develop the SMART Suite by Alcon, an innovative, digital platform that is design...

Amgen launches AMGEVITATM (biosimilar adalimumab) …

Amgen (NASDAQ:AMGN) announced that AMGEVITATM, a biosimilar to adalimumab, will launch in markets across Europe beginning on Oct. 16, 2018. AMGEVITA is the first adalimum...

Boehringer Ingelheim increases awareness of health…

Boehringer Ingelheim announced the start of a new self-help project in India to increase awareness of hygiene and health. On the occasion of the Global Handwashing Day 20...

Targeted drugs for advanced cancer move from speci…

Nearly 1 in 4 patients with advanced cancer, treated at Comprehensive Cancer Care Network (NCCN) centres in the US, are receiving innovative drugs matched to DNA mutation...

Novartis 5-year data in psoriatic arthritis and an…

Novartis, a leader in immuno-dermatology and rheumatology, announced today it will be presenting five-year data from the ongoing extensions of the phase III FUTURE 1 and ...

FDA approves asthma indication for Dupixent® (dupi…

The U.S. Food and Drug Administration has approved Dupixent® (dupilumab) as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years and old...

Largest census of cancer genes to help understand …

Researchers at the Wellcome Sanger Institute have created the first comprehensive summary of all genes known to be involved in human cancer, the "Cancer Gene Census". Des...

Diets rich in fish oil could slow the spread and g…

Omega-3 fatty acids, such as those typically contained in fish oil, may suppress the growth and spread of breast cancer cells in mice. This is according to a new study in...

Novartis announces clinical collaboration with Pfi…

Novartis announced today that it has entered into a clinical development agreement with Pfizer which will include a study combining tropifexor and one or more Pfizer comp...