fasting for two days protects normal cells from chemotherapy(in mice)humantrialsbegin

[Lani]

A New Way to Fight Cancer: Instead of a silver bullet to kill cancer cells, USC biologists discover a way to protect all other cells against chemotherapy
[University of Southern California]
Fasting for two days protects healthy cells against chemotherapy, according to a study appearing online the week of March 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 USC Davis School of Gerontology and USC College.
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 was 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 UCLA.
"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.


: ABSTRACT: Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy
[Proceedings of the National Academy of Sciences]
Strategies to treat cancer have focused primarily on the killing of tumor cells. Here, we describe a differential stress resistance (DSR) method that focuses instead on protecting the organism but not cancer cells against chemotherapy. Short-term starved S. cerevisiae or cells lacking proto-oncogene homologs were up to 1,000 times better protected against oxidative stress or chemotherapy drugs than cells expressing the oncogene homolog Ras2val19. Low-glucose or low-serum media also protected primary glial cells but not six different rat and human glioma and neuroblastoma cancer cell lines against hydrogen peroxide or the chemotherapy drug/pro-oxidant cyclophosphamide. Finally, short-term starvation provided complete protection to mice but not to injected neuroblastoma cells against a high dose of the chemotherapy drug/pro-oxidant etoposide. These studies describe a starvation-based DSR strategy to enhance the efficacy of chemotherapy and suggest that specific agents among those that promote oxidative stress and DNA damage have the potential to maximize the differential toxicity to normal and cancer cells.

[SoCalGal]

Thanks for posting this Lani. I just love when friends call me with information (like last night - calls about a "cure" by fasting - no mention of mice) and then the actual info is posted on our site. Reminds me of how lucky I am for this site.

Interesting concept.

Flori

[fullofbeans]

Thanks Lani I had not seen that about fasting.

I will not talked any further about this because I will be lynched :-)

However will quickly add that the title of the article is misleading : fasting and starving are two COMPLETELY different things. When you are fasting you are using you fat stores (ketogenic diet) when you are starving the body starts using other tissues. No one should starve themselves ever, but fasting is a different metabolic adaptation.

[Mary Anne in TX]

Well, wouldn't this be a good thing! Isn't fasting now and again good for our bodies anyway! Not that I know from experience! Maybe now is a time to see! Thanks Lani!
ma

[Carol Carlson]

Dumb question...
fasting 2 days before or after chemo ???
C

[TSund]

What's the theory of why this works (at least in the mice) ??

TRS

[Lani]

My "take" on the article:

The association between mutations that activate IGF1R,
Ras, or Akt and many human cancers prompted the authors of this study to formulate the hypothesis
that normal but not cancer cells would respond to starvation or
down-regulation of Ras/Akt signaling by entering a stress-
resistance mode.

They described one of the major hallmarks of cancer
cells as having self-sufficiency of growth signals and described that
in the majority of cancers this ability to grow or remain in a growth
mode even in the absence of growth factors is provided by the
hyperactivation of one or several components of the IGF1R,
Ras, Akt, and mTor pathways.

They particularly singled out the IGF1R pathway.

Put simply, cancer often outgrows its blood supply and has the ability
to keep growing under very adverse and stressful conditions. Thus it uses means such as activating heat shock proteins, IGF1R, RAS, Akt and mTor pathways to survive such stress whereas normal cells just go into a dormant state until the "stress" passes.

These authors hope to exploit that difference

[R.B.]

VERY thought provoking.

Thank you for posting Lani and all your hard work.

Full of beans was it you who was previously looking at controlled fasts and cancer.


A full article on fasting with caveats just for interest
http://www.falconblanco.com/health/fasting.htm


An India jain with cancer who deliberately fasted herself to death
http://www.guardian.co.uk/world/2006....randeepramesh

[TSund]

This is fascinating! Thanks Lani.

TRS

[TSund]

I'd like to see a controlled study comparing the reaction of bc in mice with fasting + chemo vs fasting alone vs no fast/chemo. It would be interesting to see if the fasting itself had an effect on the cells.

[fullofbeans]

Just a quick note: rodent have a much faster metabolic rate. It may mean possibly a longuer time required (than 2 days) for humans. Just a thought..

[Bill]

Very interesting all-around. That's a great point, fullofbeans. I don't know what the ratio is between mouse/human metabolic rate, but I hope this line of study doesn't determine that the fasting ratio for effectiveness should be the same. Two days of fasting is one thing, but.......