Cancer, arthritis treatments could target same 'glue' molecule

Date: Nov-15-2013Two very different diseases, rheumatoid arthritis and some cancers, share a common

feature - an over-abundance of a "glue" molecule that helps cells stick together. Now, a new study

suggests targeting this molecule could help treat both.

Led by a team at Georgetown University Medical Center in Washington, DC, the

researchers also found drug candidates that could target the glue protein, cadherin-11. One of the

drugs is already undergoing a clinical trial.

Senior investigator Stephen Byers, a professor and molecular oncologist at Georgetown Lombardi

Comprehensive Cancer Center, says while they do not fully understand how cadherin-11 is important

for cancer progression as well as rheumatoid arthritis, they are already "rapidly translating"

their discovery for clinical use.

The study will be published in the journal Oncotarget.

Cadherin-11 over-expressed in breast and brain cancers

The researchers found that the glue molecule is over-expressed in around 15% of breast cancers,

and in many glioblastomas - tumors that form in the glue-like supportive tissue of the brain.

Prof. Byers says:

"What most of these cancers all have in common is cadherin-11 and a poor prognosis, with no

effective therapies.

Cadherin-11 expression is required for tumors to grow. If it is blocked, the cancers in cell

line studies and in animals just stop growing - which is really quite striking."

Prof. Byers believes the glue protein is also involved in the development of pancreatic

cancer.

In 2011, another group of US researchers reported that another glue protein, N-cadherin, could

serve as a drug target to delay

metastatic pancreatic cancer.

Finding drugs to target cadherin-11 in cancer and arthritis

Prof. Byers and his team at Georgetown have developed a small molecule agent to shut down cadherin-11 in

cancer.

By screening drugs already on the market, the Georgetown team has already found that Celebrex, a

well-known arthritis drug, has a similar effect. However, it could not be used in its current form

to target cadherin-11 in cancer because it would be too toxic at the level needed to tackle the

glue protein.

The study also reports how an antibody, designed by study author Dr. Michael Brenner

of Harvard University, can block cadherin-11 in rheumatoid arthritis. This was demonstrated in

animals with tumors that were making the glue protein.

Another study author, Lawrence Shapiro, at Columbia University, is building a crystal structure

of cadherin-11 and is now working with the team to work out how it binds to Celebrex and other

small molecule drug candidates.

The team has also sought funding to help them look for what drugs, such as anti-inflammatories, have

in common that might help them protect against cancer and other conditions.

Prof. Byers and some of his co-authors are inventors on patent applications filed by Georgetown

University that are linked to the study, and Dr. Brenner is founder of Adheron Therapeutics, which

develops cadherin-11 antibodies for treating rheumatoid arthritis and cancer.

Written by Catharine Paddock PhD

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