Findings lay groundwork for human clinical trial planned for August 2016
A new scientific study has identified why colorectal cancer cells depend on a specific nutrient, and a way to starve them of it. Over one million men and women are living with colorectal cancer in the United States. The National Cancer Institute estimates 4.5% of all men and women will be diagnosed with the cancer during their lifetime, making it the third most common non-skin cancer.
In the study published online in Nature Communications, researchers showed how certain colorectal cancer cells reprogram their metabolism using glutamine, a non-essential amino acid. Many cancer cells rely on glutamine to survive. How they become so dependent on the molecule is hotly debated in the field.
Researchers studied a subset of colorectal cancer cells containing a genetic mutation called PIK3CA. This mutation is located in a gene critical for cell division and movement, and is found in approximately one third of all colorectal cancers. The mutation is also the most commonly identified genetic mutation across all cancers, making the results of the study universally appealing.
Researchers were interested in determining whether or not the common PIK3CA mutation contributes to changes in cancer cell metabolism, such as how nutrients like glutamine are processed. Normally, glutamine is broken down by cancer cells into several other molecules with the help of specific enzymes. This complicated system helps produce adenosine triphosphate, the energy currency of all cells, and other molecules critical for colorectal cancer cell growth.
The researchers found that colorectal cells with the PIK3CA mutation broke down significantly more glutamine than cells without the mutation. The researchers identified several enzymes involved in the process that are more active in the mutant cancer cells than in other cell types, explaining the increased need for glutamine. These enzymes become overactive in the mutant cancer cells due to a cascade of signals led by the protein encoded by mutant PIK3CA gene. This finding represents a novel and important link between the common PIK3CA mutation and altered glutamine metabolism in cancer cells.
Zhenghe John Wang, PhD, professor of genetics and genome sciences and co-leader of the Cancer Genetics Program at Case Western Reserve University School of Medicine helped lead the study. “In layman’s terms, we discovered that colon cancers with PIK3CA oncogenic mutations are addicted to glutamine, a particular nutrient for cancer cells. We also demonstrated that these cancers can be starved to death by depriving glutamine with drugs.”
When the researchers lowered the amount of glutamine available to mutant cancer cells growing in laboratory dishes, the cancer cells died. This discovery led the team to investigate the effects of blocking glutamine availability in mice with colorectal cancer tumors containing the common PIK3CA mutation. Wang and colleagues found that exposing these mice to a compound that blocks glutamine metabolism consistently suppressed tumor growth. They did not observe the same effect on tumors without the mutation. Together, these results provide a promising new therapeutic avenue to suppress growth of colorectal tumors with the PIK3CA mutation. The researchers have filed a patent application based on the unique mechanism of tumor suppression they have identified and the work is available for licensing.
“This study provides the basis for a colon cancer treatment clinical trial that will be started in the summer at the University Hospitals Seidman Cancer Center,” according to Neal Meropol, MD, Dr. Lester E. Coleman, Jr. Professor of Cancer Research and Therapeutics, chief of the division of hematology and oncology, and principal investigator for the trial. The phase I/II study will test the effects of a glutamine metabolism inhibitor in patients with advanced colorectal tumors.
The Latest on: Colorectal cancers
via Google News
The Latest on: Colorectal cancers
- Pelé hospitalized due to colon tumor, to be released in dayson December 8, 2021 at 11:33 pm
Pelé was briefly put in intensive care after surgery on his colon. He was discharged on Sept ... staying out of the public eye following the cancer-related death of his brother, Jair, in March ...
- Pelé Hospitalized For Cancer Treatment In Brazil, Second Time This Yearon December 8, 2021 at 10:38 pm
Arguably the greatest soccer player of all time, Pelé, was admitted to Sao Paulo’s Hospital Albert Einstein on Wednesday according to his doctors. It is the second time in the past few ...
- Pelé hospitalised for a second time as Brazilian football legend continues treatment for colon canceron December 8, 2021 at 8:08 pm
Doctors in Sao Paulo say Brazilian football legend Pelé is expected to be released in the next couple of days after being hospitalised for a second time as he continues to battle colon cancer.
- Study raises renewed alarm about missed cancer diagnoses during pandemicon December 8, 2021 at 2:37 pm
Oncologists have been warning about dangerous gaps in cancer care since the start of the COVID-19 pandemic. Now, a nationwide study based on data from Veterans Affairs hospitals is raising new alarms.
- colon canceron December 8, 2021 at 2:22 pm
According to a report from TMZ, soccer legend Pele is currently undergoing chemotherapy in a hospital in Brazil just months after being diagnosed with colon cancer. Visit streaming.thesource.com for ...
- SOURCE SPORTS: Soccer Legend Pele Undergoing Chemo Treatments For Colon Canceron December 8, 2021 at 1:50 pm
Soccer Legend Pele Undergoing Chemo Treatments For Colon Cancer Soccer Legend Pele Undergoing Chemo Treatments For Colon Cancer ...
- Soccer great Pele hospitalized for colon cancer treatmenton December 8, 2021 at 7:33 am
Brazilian soccer legend Pele was hospitalized Wednesday in order to receive treatment for colon cancer. Sao Paulo’s Hospital Albert Einstein said the 81-year-old was in stable condition and would be ...
- Colorectal cancer screening should start at age 45 yearson December 7, 2021 at 9:39 am
(HealthDay)—Average-risk colorectal cancer (CRC) screening should start at age 45 years, according to U.S. Multi-Society Task Force on Colorectal Cancer recommendations published online Nov. 15 in ...
- Grant Allows for AI Research to Improve Rectal Cancer Treatment Responseon December 7, 2021 at 9:00 am
Backed by a three-year grant, researchers can study how to use artificial intelligence in medical imaging to improve the treatment response for rectal cancer patients.
- AI-driven medical imaging may help fight against rectal canceron December 4, 2021 at 2:51 pm
Building on its successes in applying artificial intelligence (AI) to medical imaging to enhance treatment of other diseases, a Case Western Reserve University-led team next will test its approach ...
via Bing News