MAR 23, 2015 02:45 PM PDT

New Hope for Beating Deadly Hereditary Stomach and Breast Cancers

Deadly familial stomach and lobular breast cancers could be successfully treated at their earliest stages, or even prevented, by existing drugs that have been newly identified by University of Otago cancer genetics researchers.

The researchers, led by Professor Parry Guilford, show for the first time that the key genetic mutation underlying the devastating conditions also opens them to attack through drug therapies targeting other cellular mechanisms.

There is currently no treatment for this kind of gastric cancer other than surgical removal of the stomach as a preventive measure in those identified as carrying the mutated gene. Lobular breast cancer is hard to detect by mammography and mastectomies are also undertaken by some carriers.

The researchers' findings appear in the US journal Molecular Cancer Therapeutics.

The team used genomic screening to search for vulnerabilities in the cancer cells that lack the tumour-suppressor protein E-cadherin. The genetic mutation that causes this protein to be lost is common in hereditary diffuse gastric and lobular breast cancers.

E-cadherin is not a traditional drug target for these forms of cancer because the protein is present in healthy cells but absent in malignant ones. However, Professor Guilford and his team predicted that its loss might create other vulnerabilities in these cancer cells.

Professor Guilford said the research team used an approach of searching for ‘synthetically lethal' combinations of E-cadherin loss with inactivation of other proteins, which together cause cell death.

After conducting a genome-wide functional screening of non-malignant human breast cells with, and without, E-cadherin loss, they identified a large number of such vulnerabilities that can be targeted by existing drug compounds.

PhD student and study lead author Bryony Telford said further analysis showed that the most promising avenues of attack were against G-protein coupled receptor (GPCR) signalling proteins and those involved in maintaining the cell cytoskeleton.

"We found that GPCR proteins were strikingly abundant in cells lacking E-cadherin, as were diverse types of cytoskeletal proteins," Ms Telford said.

Next, the researchers screened selected drug classes known to interfere with these proteins, and found that the E-cadherin-lacking cells proved highly sensitive to many of the compounds while their normal counterparts did not.

Professor Guilford said that the synthetic lethal effects identified are highly promising for developing early chemoprevention treatments for people who carry the E-cadherin mutation and as a result are at high risk of gastric and lobular breast cancers.

"Making such drug treatments a reality would mean delaying or completely avoiding the trauma that high-risk individuals experience by undergoing major preventive surgery at a young age," he said.

The study was undertaken in collaboration with researchers from Melbourne's Peter MacCallum Cancer Centre and the University of Melbourne. The drugs were screened at the Walter and Eliza Hall Institute's High-Throughput Chemical Screening Facility in that same city.

Professor Guilford's work was supported by the Health Research Council of New Zealand.

In the 1990s he began leading an ongoing collaboration with a large Māori family from the Bay of Plenty that identified E-cadherin as the first known gene for inherited gastric cancer.

This allowed family members to be tested for the gene and to decide whether to take preventative action. This research was originally published in the leading journal Nature in 1998 and the findings have now led to hundreds of lives being saved around the world.

Kimihauora Trust Manager Maybelle McLeod, who originally contacted the University and Professor Guilford to seek help in discovering the cause of the disease ravaging her family, said the findings are very exciting.

"The only choice at the moment for those of us at genetic risk is to undergo drastic surgery, and having your stomach removed is a hard thing to bite. This latest research holds out a new hope for a gentler way to save the lives of our affected whanau members," Ms McLeod said.

Source: University of Otago
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
You May Also Like
JUN 16, 2018
Cancer
JUN 16, 2018
Lung Cancer Rates Increasing in White and Hispanic Young Women
Lung cancer has long been tied to smoking and had a higher incidence in men than women. A new study shows rates of lung cancer are increasing in some groups of young women....
JUN 20, 2018
Cancer
JUN 20, 2018
Peruvian Plant's Unique Anti-Tumor Biological Mechanism Discovered
Plagiochiline A is a molecule that exhibits antiproliferative properties and is cytotoxic. New research outlines the unique biological mechanism valued as possible cancer therapy target....
JUN 21, 2018
Immunology
JUN 21, 2018
The Silver Tsunami: An Aging Immune System and Cancer
Why do cases of cancer become more common as we get older? Scientists interested in explaining the so-called “Silver Tsunami” phenomenon look t...
JUL 17, 2018
Health & Medicine
JUL 17, 2018
Can the Keto Diet Make Cancer Treatment More Effective?
It’s been said that “you are what you eat” but with so many diet plans and trends, it can be hard to choose. Paleo, keto, Mediterranean,...
SEP 11, 2018
Cannabis Sciences
SEP 11, 2018
New Evidence Shows Marijuana Smoke is Not the Same as Cigarette Smoke, at Least, in Terms of Lung Disease.
A recent report published in the journal Breathe by scientists in the UK suggests that chronic marijuana smoking may not cause the same deleterious effects...
SEP 20, 2018
Genetics & Genomics
SEP 20, 2018
Liquid Phase Separation may Play a Role in Cancer
Not all liquids mix, like oil and water; the phenomenon is called liquid-liquid phase separation. We're learning more about its role in cells....
Loading Comments...