Tag Archives: Mammalian target of rapamycin

Can A Diet Low In Carbs & High On Protein Help In the Fight Against Cancer?

Posted on by

Eating a low-carbohydrate, high-protein diet may reduce the risk of cancer and slow the growth of tumors already present, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

Gerald Krystal, Ph.D., Professor, Pathology & Laboratory Medicine, University of British Columbia; Distinguished Scientist, Terry Fox Laboratory, British Columbia Cancer Agency

Eating a low-carbohydrate, high-protein diet may reduce the risk of cancer and slow the growth of tumors already present, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

The study was conducted in mice, but the scientists involved agree that the strong biological findings are definitive enough that an effect in humans can be considered.

“This shows that something as simple as a change in diet can have an impact on cancer risk,” said lead researcher Gerald Krystal, Ph.D., a distinguished scientist at the British Columbia Cancer Research Centre.

Cancer Research editor-in-chief George Prendergast, Ph.D., CEO of the Lankenau Institute for Medical Research, agreed. “Many cancer patients are interested in making changes in areas that they can control, and this study definitely lends credence to the idea that a change in diet can be beneficial,” said Prendergast, who was not involved with the study.

Krystal and his colleagues implanted various strains of mice with human tumor cells or with mouse tumor cells and assigned them to one of two diets. The first diet, a typical Western diet, contained about 55 percent carbohydrate, 23 percent protein and 22 percent fat. The second, which is somewhat like a South Beach diet but higher in protein, contained 15 percent carbohydrate, 58 percent protein and 26 percent fat. They found that the tumor cells grew consistently slower on the second diet.

As well, mice genetically predisposed to breast cancer were put on these two diets and almost half of them on the Western diet developed breast cancer within their first year of life while none on the low-carbohydrate, high-protein diet did. Interestingly, only one on the Western diet reached a normal life span (approximately 2 years), with 70 percent of them dying from cancer while only 30 percent of those on the low-carbohydrate diet developed cancer and more than half these mice reached or exceeded their normal life span.

Krystal and colleagues also tested the effect of mTOR inhibitor CCI-779 (temsirolimus/Torisel®), which inhibits cell growth, and COX-2 inhibitor celecoxib (Celebrex®), which reduces inflammation, on tumor development, and found these agents had an additive effect in the mice fed the low-carbohydrate, high-protein diet.

When asked to speculate on the biological mechanism, Krystal said that tumor cells, unlike normal cells, need significantly more glucose to grow and thrive. Restricting carbohydrate intake can significantly limit blood glucose and insulin, a hormone that has been shown in many independent studies to promote tumor growth in both humans and mice.

Furthermore, a low-carbohydrate, high-protein diet has the potential to both boost the ability of the immune system to kill cancer cells and prevent obesity, which leads to chronic inflammation and cancer.

About the American Association For Cancer Research (AACR)

The mission of the AACR is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.

Sources:

Experimental Drug NVP-BEZ235 Slows Ovarian Cancer Growth in Mice; Solid Tumor Clinical Trials Ongoing

Posted on by

A study conducted recently at UCLA’s Jonsson Comprehensive Cancer Center found that experimental drug NVP-BEZ235, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

A study conducted recently at  UCLA’s Jonsson Comprehensive Cancer Center (JCCC) found that an experimental drug, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

Oliver Dorigo, M.D., Ph.D., Assistant Professor, Department of Gynecologic Oncology, Division Gynecologic Oncology, UCLA Jonnson Comprehensive Cancer Center; Member, JCCC Cancer Molecular Imaging Program Area

The Novartis Oncology drug, called NVP-BEZ235, also inhibits growth of ovarian cancer cells that have become resistant to the conventional treatment with platinum chemotherapy and helps to resensitize the cancer cells to the therapy. In addition, it enhances the effect of platinum chemotherapy on ovarian cancer cells that are still responding to the therapy, said the study’s senior author, Dr. Oliver Dorigo, an assistant professor of obstetrics and gynecology and a JCCC researcher.

“Platinum-based chemotherapy drugs are effective in treating ovarian cancers as long as the cancer cells remain sensitive to platinum,” Dorigo said. “But once the tumor becomes resistant, treating the cancer becomes very challenging. This is a significant clinical problem, since the majority of ovarian cancer patients develop resistance at some point during treatment. Breaking chemotherapy resistance is a difficult challenge, but crucial if we want to improve long-term survival for our patients.”

The study, performed on cells lines and mouse models, appears in the April 15 issue of the journal Clinical Cancer Research.

Over the last several years, Dorigo has been working in his laboratory to develop new therapies for ovarian cancer. About 22,000 American women are diagnosed each year with ovarian cancer, and more than 14,000 deaths are attributed to the disease annually. Dorigo has focused his research efforts on a pathway called PI3Kinase/Akt/mTOR, which, once activated, promotes ovarian cancer growth. The activated pathway also makes the cancer more aggressive and more likely to spread to other organs, Dorigo said, so targeting it offers great promise for more effective therapies for the disease.

In this two-year study, Dorigo and postdoctoral fellow Chintda Santiskulvong found that inhibiting two checkpoints of the pathway — PI3Kinase and mTOR — with NVP-BEZ235 decreased cancer growth, both in cell culture dishes and in mice with ovarian cancer. It also significantly increased survival in the mice, he said. More importantly, NVP-BEZ235 slowed growth of the ovarian cancer cells that had become resistant to platinum and helped to break that resistance.

“We were very encouraged to find that NPV-BEZ235 could resensitize the ovarian cancer cells to standard platinum treatment,” Dorigo said. “In addition, we found this drug to be more effective in inhibiting ovarian cancer cell growth than other drugs that target only one checkpoint, mTOR, in this pathway. We believe that NVP-BEZ235 has superior efficacy because of the dual effect on PI3Kinase and mTOR.”

The experimental drug is being tested as a single agent at the Jonsson Cancer Center in human clinical trials against other solid tumors. Researchers involved with those studies have said early results are encouraging.

John Glaspy, M.D., M.P.H., Co-Chief, Department of Medicine, Hematology/Oncology, UCLA Jonnson Comprehensive Cancer Center; JCCC Director, JCCC Clinical Research Unit; Member, Stand Up To Cancer Mangement Committee

“This is clearly a promising agent with activity in humans,” said Dr. John Glaspy, a professor of hematology–oncology and a Jonsson Cancer Center scientist involved with the studies. “We are still assessing its tolerability in patients.”

Dorigo said he hopes to initiate a clinical trial for women with ovarian cancer that tests the combination of NVP-BEZ235 with platinum chemotherapy, as he believes that the combination might be more effective than each drug alone.

The study was funded by the Ovarian Cancer Research Foundation/Liz Tilberis Scholarship, the Gynecologic Cancer Foundation/Florence and Marshall Schwid Ovarian Cancer Award, a STOP Cancer Career Development Award and the National Institutes of Health’s Women’s Reproductive Health Research Program.

About the UCLA Jonnson Comprehensive Cancer Center

UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years.

Sources:

Clinical Trial Information: