'Backwards step' reveals cancer cells are 'smart little bastards'

March 16, 2017, University of New South Wales
‘Backwards step’ reveals cancer cells are ‘smart little bastards’
Credit: Shutterstock

It may seem like a backward step, but a discovery by UNSW researchers that a new treatment for liver cancer encourages rather than reduces tumour growth provides valuable insight into the complex biology of cancer cells.

Targeting the 'Achilles' heel' of could have unintended consequences, encouraging rather than preventing tumour growth, UNSW researchers warn.

Liver cancer is the third leading cause of cancer-related death worldwide and is the fastest growing cancer in Australia.

"Many people suspect an Achilles' heel of liver cancer is a metabolic process in cells called lipogenesis, which converts sugars into fats," says Associate Professor Kyle Hoehn from UNSW. "This fat production is thought to play an important role in helping cancer cells proliferate."

While a team led by Hoehn managed to successfully block lipogenesis in the of genetically modified mice, there was an unintended consequence.

Rather than halting the growth of cancer cells as the team predicted, blocking this metabolic pathway resulted in the unexpected appearance of twice as many tumours. The surprising results were published this week in Nature Communications.

Hoehn says there are drugs currently being developed to target and block this metabolic pathway, which are considered promising treatments for liver and other cancers. He says these results might raise some concerns, at least for liver cancer.

"Our discovery was completely counterintuitive, but it clearly indicates that any treatment of liver cancer with these drugs in the future should be approached with caution, as there could be unanticipated consequences."

Understanding the Achilles' heel

When cells divide, they need to remake all of their structural components including their protective membranes made of fat, and this process is facilitated through lipogenesis.

"Lipogenesis is a hallmark of aggressive liver cancer, and patients with high lipogenesis in tumours have the worst survival rates," says Hoehn.

"Before we began this experiment, we believed that if you could knock the legs out of lipogenesis, then you could stop the cancer cells from forming or proliferating so rapidly."

This was Hoehn's hypothesis. But his team discovered the opposite.

Cancer cells survive and sneakily adapt

The team tested whether their genetically modified mice could get cancer by exposing them to DNA-damaging carcinogens and introducing a high-fat diet. These insults increase the risk of tumour development later in life.

At nine months old, they compared tumour burden of the genetically-modified mice and the mice with normal liver lipogenesis. The modified mice not only had a 2-fold increased risk of developing at least one tumour, but mutant mice that did develop tumours had twice as many tumours compared to normal mice.

"The results were very surprising," says Hoehn. "In blocking lipogenesis, we actually improved the cells' antioxidant defence system. This basically enabled the damaged, precancerous cells to survive."

So rather than seeing these mutant liver cells dying off in droves, they were actually surviving to become tumours.

Furthermore, the team found that the cancer cells quickly adapted to the loss of lipogenesis: they began to scavenge more fat from the bloodstream, and preserved this fat more efficiently by burning less of it. Thus by kicking out one leg of lipid metabolism, the others grew stronger.

"Cancer cells always seem to have a workaround," says Hoehn. "They're smart little bastards."

While on the surface it may seem like a step backward for cancer treatment, Hoehn says the discovery has revealed valuable insight into the complex biology of , and also identified a possible new target for future drugs: the mechanisms driving the antioxidant defence system or fat uptake.

Furthermore, he says the study demonstrates the necessity of the rigorous scientific testing that underpins drug development.

Explore further: Starving cancer cells by blocking their metabolism

Related Stories

Starving cancer cells by blocking their metabolism

June 14, 2016
Scientists at EPFL have found a way to starve liver cancer cells by blocking a protein that is required for glutamine breakdown—while leaving normal cells intact. The discovery opens new ways to treat liver cancer.

Tumour protein could hold key to pancreatic cancer survival

February 23, 2017
A diagnosis of pancreatic cancer is often a death sentence because current chemotherapies have little impact on the disease.

Researchers find link between common enzyme and cancer prevention

January 24, 2017
A common enzyme found in mammals that kills damaged cells before they become cancerous is being hailed as an important breakthrough in understanding the treatment of the disease.

Targeting the biological clock could slow the progression of cancer

February 16, 2017
Does the biological clock in cancer cells influence tumour growth? Yes, according to a study conducted by Nicolas Cermakian, a professor in McGill University's Department of Psychiatry.

Researchers discover new path to stop the spread of cancer

October 18, 2016
Investigators from the Research Institute of the McGill University Health Centre (RI-MUHC), and the Institute of Cancer Research, London (UK), have discovered that some cancer cells can draw blood from existing mature blood ...

New genes identified that regulate the spread of cancers

January 11, 2017
Research led by the Wellcome Trust Sanger Institute has discovered a new biological target for drugs to reduce the spread of tumours in cancer patients. Published in Nature today, the study with genetically modified mice ...

Recommended for you

Potential seen for tailoring treatment for acute myeloid leukemia

December 8, 2018
Advances in rapid screening of leukemia cells for drug susceptibility and resistance are bringing scientists closer to patient-tailored treatment for acute myeloid leukemia (AML).

Study may offer doctors a more effective way to treat neuroblastoma

December 7, 2018
A very large team of researchers, mostly from multiple institutions across Germany, has found what might be a better way to treat patients with neuroblastoma, a type of cancer. In their paper published in the journal Science, ...

Inflammatory bowel disease linked to prostate cancer

December 7, 2018
Men with inflammatory bowel disease have four to five times higher risk of being diagnosed with prostate cancer, reports a 20-year study from Northwestern Medicine.

'Chemo brain' caused by malfunction in three types of brain cells, study finds

December 6, 2018
More than half of cancer survivors suffer from cognitive impairment from chemotherapy that lingers for months or years after the cancer is gone. In a new study explaining the cellular mechanisms behind this condition, scientists ...

Scientists develop new technology for profiling unique genetic makeup of myeloma tumor cells

December 6, 2018
Cancer arises when cells lose control. Deciphering the "blueprint" of cancer cells—outlining how cancer cells hijack specific pathways for uncontrolled proliferation—will lead to more efficient ways to fight it. Joint ...

Putting the brakes on tumor stealth

December 6, 2018
New research undertaken at Monash University has shed new light on how some cancers are able to escape our immune system.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.