Researchers identify unique mechanism to remove the tumors of colorectal cancer in mice -
A new scientific study has identified why colorectal cancer cells depend on a specific nutrient, and a way to deprive them of it. More than one million men and women living with the US colorectal cancer. The National Cancer Institute estimated 4.5% of all men and women will be diagnosed with cancer during their lifetime, making it the third cancer the most common non-skin.
In the study published online in Nature Communications , the researchers showed how some colorectal cancer cells reprogram their metabolism using glutamine, a nonessential amino acid. Many cancer cells depend glutamine for survival. How they become so dependent on the molecule is hotly debated in the field.
The researchers studied colorectal cancer cell subset containing a genetic mutation called PIK3CA. This mutation is in a gene essential for cell division and movement, and is about one-third of all colorectal cancers. The mutation is also genetic mutation most commonly identified in all cancers, which makes the results of the study universally appealing.
The researchers were interested in determining whether or not the common PIK3CA mutation contributes to changes in the metabolism of cancer cells, such as how nutrients such as glutamine are processed. Normally, glutamine is decomposed by cancer cells in several other molecules using specific enzymes. This complicated system helps produce adenosine triphosphate, the energy currency of all cells, and other critical molecules for the growth of colorectal cancer cells.
The researchers found that colorectal cells with PIK3CA mutation decompose much glutamine that cells without mutation. Researchers have identified several enzymes involved in the process which are more active in the mutant cancer cells than in other cell types, which explains the increased need for glutamine. These enzymes become overactive mutant in cancer cells due to a cascade of signals conducted by the protein encoded by the gene PIK3CA mutant. This discovery represents a new and important link between PIK3CA mutation and impaired metabolism of glutamine in cancer cells.
Zhenghe John Wang, Ph.D., 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 simple terms, we discovered that colon cancers with PIK3CA oncogene mutations are addicted to glutamine, a nutrient for cancer cells. We also demonstrated that these cancers can be starved by denying glutamine with medication. "
when the researchers lowered the amount of glutamine available mutant cancer cells in laboratory culture dishes, cancer cells died. This discovery led the team to study the blocking effects of glutamine availability in mice with colorectal cancer tumors containing the common PIK3CA mutation. Wang and colleagues found that exposure of these mice a compound that blocks the metabolism of systematically suppressed tumor growth glutamine. They do not respect the same effect on tumors without mutation. Together, these results provide a promising new therapeutic approach to suppress the growth of colorectal tumors with PIK3CA mutation. The researchers have filed a patent application based on the unique mechanism of tumor suppression, they identified and work is available for licensing.
"This study provides the basis for a clinical trial to be launched colon cancer treatment in the summer at the University Hospitals Seidman Cancer Center," according to Neal Meropol, MD, Dr. Lester E. Coleman, professor Jr. of cancer research and therapeutics, chief of the division of hematology and oncology, and principal investigator of the trial. Phase I / II study will test the effects of glutamine metabolism inhibitor in patients with advanced colorectal tumors.
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