About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Study of Stomach Cancer may Hasten Better Therapies

by Bidita Debnath on July 24, 2014 at 11:21 PM
Font : A-A+

 Study of Stomach Cancer may Hasten Better Therapies

Scientists, including researchers at Dana-Farber Cancer Institute have identified four subtypes of tumors based on shared mutations and other molecular abnormalities, in a massive effort to catalog the molecular causes of stomach cancer.

They say the new classification promises to advance clinical research to develop improved therapies for the third-leading cancer killer worldwide.

Advertisement

In a report in Nature, investigators of The Cancer Genome Atlas Research Network said they analyzed 295 samples of gastric (stomach) cancer, looking for ways to sort them into groups with similar key DNA defects and molecular aberrations. It was extremely important, they said, to identify categories that would be useful in guiding therapy for patients.

"We clearly converged on four groups of gastric cancer with distinct features and classes of molecular alterations," said Adam Bass, MD, the corresponding author of the report. He is director for translational research for the Center for Esophageal and Gastric Cancer at Dana-Farber, and an associate member of the Broad Institute of MIT and Harvard.
Advertisement

Grouping the cancers in this way will help researchers enroll patients in clinical trials that test drugs designed to target their particular stomach cancer subtype, said Bass. There is an urgent need for new therapies he said, because "these are aggressive cancers and the five-year survival rate is between 20 and 25 percent."

Gastric adenocarcinomas - the vast majority of stomach cancers - cause more than 700,000 deaths worldwide each year. The American Cancer Society estimates that 22,220 cases will be diagnosed in the United States in 2014, with about 10,990 deaths. Stomach cancer is mainly a disease of elderly people. Infection with the bacterium Helicobacter pylori (H pylori) is a major cause. Other risk factors include diet, smoking, geography and ethnicity, and some inherited cancer syndromes. Research on the biology of stomach cancer and the development of new therapies has been difficult because of its diversity and the presence of different pathological forms. "It is a very heterogeneous disease, but most clinical trials have taken a one-size fits all approach and attempted to find a single optimal therapy to apply across gastric cancer," said Bass. "This traditional approach has likely contributed to the slow progress we have made in treatments for this cancer."

The new study is part of The Cancer Genome Atlas (TCGA) project, a federally funded initiative that involves large international groups of researchers and centers that are cataloging genomic characteristics across a spectrum of different forms of cancer with the goal of creating a new foundation of understanding of these cancers, enabling improvements in diagnosis, treatment and prevention.

The gastric cancer research team collected fresh, frozen tissue specimens and blood samples from 295 patients from hospitals around the world who had not been treated with chemotherapy or radiation. The tissue specimens were analyzed with six different molecular analysis technologies. Among them: sequencing the protein-coding DNA in each tumor; detecting mutations or missing or extra copies of gene sequences; determining the methylation status of DNA (chemical changes affecting gene activity); sequencing the messenger RNA and microRNA in the tumors, and assessing expression of key proteins.

When computational methods were applied to the large amount of resulting data, the cancers fell into four subtypes:

  • Tumors containing the Epstein-Barr virus (EBV), along with mutations in the PIK3CA gene pathway, extreme DNA hypermethylation, and extra copies of PD-L1 and PD-L2 genes. This group made up about 10 percent of the cancers. Bass said these results suggest that inhibitors of the PI3-K pathway could have great utility in these cancers. Furthermore, he said, the findings of elevated levels of PD-L1 and PD-L2, key regulators of the immune response, suggest that emerging immunotherapy agents be tested in these patients.

  • Tumors in which malfunctioning DNA repair mechanisms cause a high rate of mutations - many of them leading to potential activation of cancer-related signaling proteins that can be targeted with novel precision drugs. About 20 percent of tumors fell into this subtype.

  • The largest category of tumors, making up about half of the cancer specimens, was termed "chromosomally unstable." These cancer cells contained a jumble of extra or missing pieces of genes and chromosomes. Bass said these tumors "have a striking number of genomic amplifications [extra copies] of key cancer-promoting genes" for which targeted therapies exist or are in development. This subtype of tumor is frequently found in the junction between the stomach and the esophagus - a type of stomach cancer that has been dramatically increasing in the United States, he said.

  • The fourth group of tumors was termed "genomically stable" as they lacked the molecular features of the other three types. These tumors, making up 20 percent of the specimens were largely those of a specific class of gastric cancer called diffuse-type tumors.
"These tumors are especially deadly because of their ability to metastasize rapidly and because we lack effective therapies," said Bass. The team identified a novel set of genomic alterations in a pathway called the RHOA signaling pathway in about 30 percent of these tumors. "This finding result opens up an entirely new line of research to allow us to investigate what underlies this deadly form of gastric cancer and to ultimately develop new therapies," said Bass.

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Health Benefits of Sea Buckthorn
Contraceptive Pills in Polycystic Ovary Syndrome (PCOS) Curtail Type 2 Diabetes Risk
Mushroom May Help Cut Down the Odds of Developing Depression
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Gastroscopy Gastric Cancer Cancer and Homeopathy Cancer Facts Cancer Tattoos A Body Art Peritoneal Cancer Common Lifestyle Habits that Cause Diseases Health Benefits of Dandelion Plant COX - 2 Inhibitors 

Recommended Reading
Research Provides New Hope for Early Detection of Stomach Cancer
Research done at the University of Adelaide has provided new hope for the early detection of ......
Diagnostic Pill That Could Help Detect Stomach Cancer Developed
A tiny capsule that could carry out a chemical analysis of the contents of one's stomach and ......
High-salt Diet Increases Stomach Cancer Risk
A diet high in salt content and ulcer bacteria increase the risk of gastric cancer, say ......
Get Rid of Bacteria to Prevent Stomach Cancer
Australian Nobel laureate Robin Warren said get rid of bacteria and improve public health to ......
Common Lifestyle Habits that Cause Diseases
Cigarette smoking, unhealthy diets, overuse of alcohol, and physical inactivity are some of the most...
COX - 2 Inhibitors
What are COX–2 Inhibitors? Why are they safer compared to NSAIDs and which conditions are best trea...
Gastric Cancer
Stomach (gastric) cancer develops from the stomach lining. It is the third most common cause for can...
Gastroscopy
Gastroscopy is a diagnostic test that enables the doctor to look inside of the esophagus, stomach, a...
Health Benefits of Dandelion Plant
What is dandelion? Dandelion greens are nutrition powerhouses with a wide range of health benefits. ...
Peritoneal Cancer
Peritoneal cancer is a rare cancer that develops in the peritoneum. Peritoneal cancers may be primar...
Tattoos A Body Art
Tattoos are a rage among college students who sport it for the ‘cool dude’ or ‘cool babe’ look...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use