Scientists identify cancer specific cell for potential targeted treatment of gastric cancer

April 23, 2014, National University of Singapore

New research by the Cancer Science Institute of Singapore and National University Hospital Singapore suggests that a variant of a cell surface protein is an ideal target for developing drugs to treat gastric cancer

A team of scientists led by a researcher from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has identified the cancer specific stem cell which causes . This discovery opens up the possibility of developing new drugs for the treatment of this disease and other types of cancers.

The research group, led by Dr Chan Shing Leng, Research Assistant Professor at CSI Singapore, demonstrated for the first time that a cancer-specific variant of a cell surface protein, CD44v8-10, marks gastric cancer stem cells but not normal cells. Conceptualised by Dr Chan and Associate Professor Jimmy So, a Senior Consultant from the Department of Surgery at the National University Hospital Singapore, the study is also the first to be conducted with human gastric tissue specimens and took five years to complete. This novel study will be published in the research journal Cancer Research, the official journal of American Association of Cancer Research, in May 2014.

Gastric cancer is a major cause of cancer-related deaths worldwide, with low survival and high recurrence rates for patients with advanced disease. New therapies for the treatment of gastric cancer are urgently needed.

How CD44v8-10 serves as a biomarker

Many cancer cell types express high levels of a known as CD44. This protein marks cancer stem cells that are thought to be responsible for resistance to current cancer therapy and tumour relapse. There are many forms of CD44 and the standard form of CD44, CD44s, is found in high abundance on normal blood cells. It was previously not known which form of CD44 is found on cancer stem cells. This is critical as an ideal cancer target should mark only cancer cells but not normal cells.

Research by the team and other scientists in the field has led to the hypothesis that the growth of gastric cancer may be driven by cancer stem cells. In this study, the researchers analysed 53 patient tissue samples in conjunction with patient-derived xenograft models which are derived from intestinal type gastric cancer. The team is one of the few groups in the world to have a relatively large collection of patient-derived xenograft models for gastric cancer and the first to use these models for identification of gastric cancer stem cells. A total of eight cancer cell lines were used in this study, including six new cell lines which were established by the researchers.

The scientists discovered a cancer-specific CD44 variant, CD44v8-10 marks gastric cancer stem cells but not normal cells. CD44v8-10 promotes cancer cell growth and it is significantly more abundant in gastric tumour sites compared to normal gastric tissue, which makes it easily detectable. The findings results suggest that CD44v8-10 is an ideal target for developing clinical therapeutics against gastric cancer stem cells. As CD44v8-10 is cancer specific, it may also be used as a biomarker for screening and diagnosis of gastric cancer. This is significant as biomarkers for early detection of gastric cancer are currently not available and doctors rely on endoscopy for the screening and diagnosis of this disease.

Said Dr Chan, "With our findings, we can now work on developing drugs that would recognise and attack the cancer only, reducing the side effects on . With additional funding, we aim to have a drug that can show efficacy in our models within three years."

"We are very excited about this discovery. It may explain why gastric cancer patients develop cancer relapse after chemotherapy as conventional chemotherapy mainly targets the common cancer cells. Hence, if we can find drugs that can target these gastric , we may improve the patients' outcome in the future," said Assoc Prof So, who is also a faculty member from the Department of Surgery at the NUS Yong Loo Lin School of Medicine.

Further research

In the next phase of their research, the scientists aim to develop an antibody drug that targets CD44v8-10. The research team also hopes to establish more patient-derived xenograft models to achieve extensive coverage of the patient spectrum in Singapore as the level of CD44v8-10 varies among patients. These xenograft models play an important role as pre-clinical models for evaluating potential therapeutics that target CD44v8-10.

Explore further: New AGA/GCF research grant to fund exploration of the development of gastric cancer

Related Stories

New AGA/GCF research grant to fund exploration of the development of gastric cancer

March 11, 2014
The American Gastroenterological Association (AGA) Research Foundation and the Gastric Cancer Foundation (GCF) are pleased to announce that the first AGA–Gastric Cancer Foundation Research Scholar Award in Gastric and Esophageal ...

New hope for early detection of stomach cancer

March 17, 2014
(Medical Xpress)—University of Adelaide research has provided new hope for the early detection of stomach cancer with the identification of four new biomarkers in the blood of human cancer patients.

International study shows efficacy of new gastric cancer drug

October 2, 2013
This international trial, published in The Lancet, is one of the largest phase III trials in second-line treatment of gastric cancer. Standard care for advanced gastric cancer, known as first-line treatment, is based on chemotherapy, ...

Ironing out the link between H. pylori infection and gastric cancer

December 21, 2012
H. pylori frequently causes gastric ulcers and is also one of the greatest risk factors for gastric cancer. H. pylori infection is also associated with another gastric cancer risk factor, iron deficiency.

Peptide derived from cow's milk kills human stomach cancer cells in culture

November 7, 2013
New research from a team of researchers in Taiwan indicates that a peptide fragment derived from cow's milk, known as lactoferricin B25 (LFcinB25), exhibited potent anticancer capability against human stomach cancer cell ...

Study reveals optimal interval for stomach cancer screening

July 16, 2012
A new study has determined how often people should get screened for gastric or stomach cancer in high-risk regions of the world. Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the ...

Recommended for you

New approach attacks 'undruggable' cancers from the outside in

January 23, 2018
Cancer researchers have made great strides in developing targeted therapies that treat the specific genetic mutations underlying a patient's cancer. However, many of the most common cancer-causing genes are so central to ...

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.