A new way to fight cancer: the silver shield

March 31, 2008

Fasting for two days protects healthy cells against chemotherapy, according to a study appearing online the week of Mar. 31 in PNAS Early Edition. Mice given a high dose of chemotherapy after fasting continued to thrive. The same dose killed half the normally fed mice and caused lasting weight and energy loss in the survivors.

The chemotherapy worked as intended on cancer, extending the lifespan of mice injected with aggressive human tumors, reported a group led by Valter Longo of the University of Southern California.

Test tube experiments with human cells confirmed the differential resistance of normal and cancer cells to chemotherapy after a short period of starvation.

Making chemotherapy more selective has been a top cancer research goal for decades. Oncologists could control cancers much better, and even cure some, if chemotherapy were not so toxic to the rest of the body.

Experts described the study as one of a kind.

“This is a very important paper. It defines a novel concept in cancer biology,” said cancer researcher Pinchas Cohen, professor and chief of pediatric endocrinology at the University of California, Los Angeles.

“In theory, it opens up new treatment approaches that will allow higher doses of chemotherapy. It’s a direction that’s worth pursuing in clinical trials in humans.”

Felipe Sierra, director of the Biology of Aging Program at the National Institute on Aging, said: “This is not just one more anti-cancer treatment that attacks the cancer cells. To me, that’s an important conceptual difference.”

Sierra was referring to decades of efforts by thousands of researchers working on “targeted delivery” of drugs to cancer cells. Study leader Longo focused instead on protecting all the other cells.

Sierra added that progress in cancer care has made patients more resilient and able to tolerate fasting, should clinical trials confirm its usefulness.

“We have passed the stage where patients arrive at the clinic in an emaciated state. Not eating for two days is not the end of the world,” Sierra said.

“This could have applicability in maybe a majority of patients,” said David Quinn, a practicing oncologist and medical director of USC Norris Hospital and Clinics. He predicted that many oncology groups would be eager to test the Longo group’s findings, and advised patients to look for a clinical trial near home.

Longo, an anti-aging researcher who holds joint appointments in gerontology and biological sciences at USC, said that the idea of protecting healthy cells from chemotherapy may have seemed impractical to cancer researchers, because the body has many different cells that respond differently to many drugs.

“It was almost like an idea that was not even worth pursuing. In fact it had to come from the anti-aging field, because that’s what we focus on: protecting all cells at once,” Longo said.

“What really was missing was a perspective of someone from the aging field to give this field a boost,” UCLA’s Cohen said.

The idea for the study came from the Longo group’s previous research on aging in cellular systems, primarily lowly baker’s yeast.

About five years ago, Longo was thinking about the genetic pathways involved both in the starvation response and in mammalian tumors.

When the pathways are silenced, starved cells go into what Longo calls a maintenance mode characterized by extreme resistance to stresses. In essence the cells are waiting out the lean period, much like hibernating animals.

But tumors by definition disobey orders to stop growing because the same genetic pathways are stuck in an “on” mode.

That could mean, Longo realized, that the starvation response might differentiate normal and cancer cells by their stress resistance, and that healthy cells might withstand much more chemotherapy than cancer cells.

The shield for healthy cells does not need to be perfect, Longo said. What matters is the difference in stress resistance between healthy and cancerous cells.

During the study, conducted both at USC and in the laboratory of Lizzia Raffaghello at Gaslini Children’s Hospital in Genoa, Italy, the researchers found that current chemotherapy drugs kill as many healthy mammalian cells as cancer cells.

“(But) we reached a two to five-fold difference between normal and cancer cells, including human cells in culture. More importantly, we consistently showed that mice were highly protected while cancer cells remained sensitive,” Longo said.

If healthy human cells were just twice as resistant as cancer cells, oncologists could increase the dose or frequency of chemotherapy.

“We were able to reach a 1,000-fold differential resistance using a tumor model in baker’s yeast. If we get to just a 10-20 fold differential toxicity with human metastatic cancers, all of a sudden it’s a completely different game against cancer,” Longo said.

“Now we need to spend a lot of time talking to clinical oncologists to decide how to best proceed in the human studies.”

Edith Gralla, a research professor of chemistry at UCLA, said: “It is the sort of opposite of the magic bullet. It’s the magic shield.”

Source: University of Southern California

Explore further: Researcher develops effective fasting tool against cancer

Related Stories

Researcher develops effective fasting tool against cancer

August 30, 2016
Fasting is a tool for effective cancer treatment. A new study shows that the right diet in combination with chemotheraphy not only protect the body's immune system, it also turns it against cancer cells.

Fasting and less-toxic cancer drug may work as well as chemotherapy

March 30, 2015
Fasting in combination with chemotherapy has already been shown to kill cancer cells, but a pair of new studies in mice suggests that a less-toxic class of drugs combined with fasting may kill breast, colorectal and lung ...

Strategies to mimic fasting during chemotherapy enhance anticancer T cell activity in mice

July 11, 2016
Fasting is known to increase positive outcomes during cancer treatment, and now two independent studies in mice show that fasting, either through diet or drugs, during chemotherapy helps increase the presence of cancer-killing ...

10-fold life span extension reported in simple organism

January 11, 2008
Biologists have created baker's yeast capable of living to 800 in yeast years without apparent side effects.

Fasting triggers stem cell regeneration of damaged, old immune system

June 5, 2014
In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study in the June 5 issue of the Cell Press journal Cell Stem Cell shows that cycles of prolonged fasting not ...

Fasting during chemotherapy may offset spikes in blood sugar caused by cancer-fighting drugs

March 31, 2017
A short-term fast appears to counteract increases in blood sugar caused by common cancer drugs, protecting healthy cells in mice from becoming too vulnerable to chemotherapy, according to a new study from USC researchers.

Recommended for you

Pushing closer to a new cancer-fighting strategy

December 11, 2018
A molecular pathway that's frequently mutated in many different forms of cancer becomes active when cells push parts of their membranes outward into bulging protrusions, Johns Hopkins researchers report in a new study. The ...

Scientists have identified and modelled a distinct biology for paediatric AML

December 11, 2018
Scientists have identified and modelled a distinct biology for paediatric acute myeloid leukaemia, one of the major causes of death in children.

HER2 mutations can cause treatment resistance in metastatic ER-positive breast cancer

December 11, 2018
Metastatic breast cancers treated with hormone therapy can become treatment-resistant when they acquire mutations in the human epidermal growth factor receptor 2 (HER2) that were not present in the original tumor, reports ...

Loss of two genes drives a deadly form of colorectal cancer, reveals a potential treatment

December 11, 2018
Colorectal cancers arise from earlier growths, called polyps, found on the inner surface of the colon. Scientists are now learning that polyps use two distinct molecular pathways as they progress to cancer, called the "conventional" ...

Taking uncertainty out of cancer prognosis

December 11, 2018
A cancer diagnosis tells you that you have cancer, but how that cancer will progress is a terrifying uncertainty for most patients. Researchers at Cold Spring Harbor Laboratory (CSHL) have now identified a specific class ...

Successful anti-PD-1 therapy requires interaction between CD8+ T cells and dendritic cells

December 11, 2018
A team led by a Massachusetts General Hospital (MGH) investigator has found that successful cancer immunotherapy targeting the PD-1 molecule requires interaction between cytotoxic CD8+ T cells, which have been considered ...

3 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

MikeMarianiMD,FAAP
4 / 5 (1) Mar 31, 2008
Fascinating! While the oncological impact is exciting, fasting for 2 days?
Hello? I won't do that while I am well. Surely, psychopharmacological dimensions to this therapy are critical to it's success. Perhaps these are so elementary, they are not discussed. I do believe that pronounced sedation is unlikely to impact the impact of the fast on the cancers.
I hope this turns out to be as great as it sounds!!!!
superhuman
4 / 5 (1) Mar 31, 2008
Thats an amazing discovery, if it works in humans (and the chances are high imho) its surly worth a Nobel prize!
dsmith
not rated yet Apr 01, 2008
They should give a try to multigram trans-resveratrol supplementation, seeing as calorie restriction does similar stress resistance increases in cells.

The resveratrol attacks, prevents, inteferes with, and weakens cancers cells at all stages while strengthening normal healthy cells against stress(yes even human cells, iirc, in vitro showed it tripled survival to gamma radiation exposure.).

IT makes cancer more vulnerable to chemo and to radiation, iirc, besides outright killing some of such cells. While protecting the rest of the normal tissue from all sorts of stresses.

The question is bio-availability in vivo in humans, but this can be injected, and megadosed safely bypassing any bioavailability problem.

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.