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
- Average-risk individuals may prefer stool-based test over colonoscopy for cancer screeningon April 22, 2021 at 4:39 pm
When given a choice, most individuals with an average risk of colorectal cancer said they would prefer a stool-based screening test for colorectal cancer over colonoscopy, the method most often ...
- Scar Stories: The Toll of Colon Canceron April 22, 2021 at 11:06 am
After the death of Chadwick Boseman from colon cancer, Ibram X. Kendi and more felt moved to speak about their own fight. Here, seven patients and survivors bare their wounds.
- A new study identifies interleukin 11 as a marker of cancer-associated fibroblastson April 22, 2021 at 8:01 am
IL-11 is known to promote the development of colorectal cancer in humans and mice, but when and where IL-11 is expressed during cancer development is unknown. "To address these questions ...
- Clinicopathological factors associated with synchronous distant metastasis and prognosis of stage T1 colorectal cancer patientson April 22, 2021 at 6:02 am
It is rare and understudied for patients with stage T1 colorectal cancer to have synchronous distant metastasis. This study was to determine the clinicopathological factors associated with distant ...
- Here's What Every Guy Should Know About Colon Canceron April 22, 2021 at 5:00 am
Colon cancer is the second-leading cause of cancer death in men and women, and the third most common cancer diagnosis. On top of that, alarmingly, an increasing number of young people are being ...
- Colorectal Cancer Screening Market Latest Size, Growth Factors and Major Segments, Forecast Research Report, Fortune Business Insightson April 21, 2021 at 9:37 pm
Colorectal Cancer ScreeningMarket | 2021 Size, Growth, Share, Cap, Regional Analysis With Global Industry Forecast To ...
- Surgeon: COVID disruption impacting early detection of colorectal canceron April 21, 2021 at 5:14 pm
Now in remission after being diagnosed with stage 2 colon cancer in late 2019, the Clear Lake resident undergoes biannual checkups to make sure his cancer has not returned. Every clear scan and every ...
- Trey Mancini signs ball for O's fan fighting colon canceron April 21, 2021 at 4:58 pm
Orioles first baseman Trey Mancini continues to be one of the biggest inspirations in baseball after returning from a year fighting colon cancer. His recovery process has been fol ...
- Neoadjuvant Regimen Tops Standard for Locally Advanced Rectal Canceron April 20, 2021 at 2:08 pm
Adding neoadjuvant chemotherapy to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer led to better disease-free survival (DFS) and less toxicity as compared with a standard ...
- Colorectal Cancer: What You Should Know About Screeningon April 20, 2021 at 11:56 am
There are several FDA-reviewed and approved or cleared choices for colorectal cancer screening. Find out which one is best for you.
via Bing News