Protein folding becomes cancer treatment target

December 3, 2013, Cancer Research UK
Prevent proteins folding and you may stop cancer growing

(Medical Xpress)—A molecule that helps cancer cells to keep dividing could be a promising target for new treatments, according to research published in the journal Oncogene.

The Cancer Research UK-funded study looked at molecules in our cells that make sure proteins are folded properly, known as chaperones. The researchers examined the chaperone HSP90, responsible for helping to fold proteins that control . They revealed crucial new details about how the chaperone works alongside a partner – called CDC37 – to carry out its job and keep cancer cells growing.

Until now, researchers have focused their efforts on designing drugs to block CDC37's role in folding by disrupting the way it interacts with HSP90. But this new research, carried out by scientists at the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, London, reveals the two players can act independently when folding cancer-causing proteins, thus changing the view about how best to attack them.

Proteins are the 'work-horses' of cells, carrying out all kinds of jobs, from supporting a cell's structure to creating energy, sending messages and repairing damaged DNA. In order to function correctly, proteins need to have a certain shape – this is where chaperones step in to help. Chaperones fold proteins into the right shape and keep them stable, which is critical for them to work properly.

Cancer cells divide very rapidly and the proteins that perform this task and keep the cells growing rely upon chaperones to fold correctly. By blocking the machinery that folds the proteins into the right shape, it should be possible to stop the cancer cells from growing. And because cancer cells are far more reliant on chaperones than normal cells, it should be possible to attack tumours without harming healthy tissue.

The same team has already been successful in discovering drugs that work on HSP90, with one of these – AUY922 – showing promise in the clinic. But chaperones do not operate alone. They rely on partner molecules, such as CDC37, so targeting these might be an alternative way to stop the chaperones working.

Study author Professor Paul Workman, Cancer Research UK Life Fellow and deputy chief executive of The Institute of Cancer Research (ICR) said: "Chaperones help stabilise the proteins that cancer cells need to divide and multiply, which means they present an exciting target for new treatments. We've been successful in designing drugs that work against the HSP90 chaperone and these look very promising in the clinic.

"Our new study has revealed critical details about the way HSP90 and CDC37 work together, which could be fundamental in designing drugs that target this partnership. It shows for the first time that, although both are needed to fold cancer-causing proteins, HSP90 and CDC37 do not necessarily have to bind to each other directly and so cancer cells can get around blocking their interaction. We now know that we'll need to develop new approaches."

Dr Kat Arney, science information manager at Cancer Research UK, said: "There's still a lot to learn about the various roles played by chaperones and their supporting molecules. But if we widen our net to target more of these molecules we may discover new ways of stopping cancer cells from multiplying.

"Because they divide rapidly, are heavily dependent on chaperones, providing a weakness for us to target. Drugs that block these molecules might give us a way to stop cancers from growing any further and, combined with other treatments, give patients an even better chance of beating the disease."

Explore further: Indian plant could play key role in death of cancer cells

Journal reference: Oncogene search and more info website

Provided by: Cancer Research UK search and more info website


Related Stories

Indian plant could play key role in death of cancer cells

February 14, 2013
Scientists at the Georgia Regents University Cancer Center have identified an Indian plant, used for centuries to treat inflammation, fever and malaria, that could help kill cancer cells.

Blocking 'lock and key' site of lung cancer proteins could lead to new treatments

November 12, 2013
A Cancer Research UK study reveals that stopping two essential lung cancer proteins from joining together at their 'lock and key' site could lead to new treatments for the disease. The research is published in the journal ...

Scientists define cellular pathway essential to removing damaged mitochondria

August 23, 2011
In a joint research effort with researchers at St. Jude Children's Research Hospital, and with help from scientists at The University of Pennsylvania, The University of Minnesota, and the National Institutes of Health, investigators ...

Potential brain tumour drug can distinguish cancer cells from healthy ones

October 31, 2013
A potential new drug, already in clinical development, can stop brain tumour cells growing while leaving healthy cells alone, according to new research published today (Wednesday) in PLOS ONE.

New drug extends advanced lung cancer survival

June 3, 2013
A new drug can help advanced lung cancer patients live longer and may aid in treating other kinds of cancer, researchers said Monday.

Recommended for you

Targeting telomeres to overcome therapy resistance in advanced melanoma

March 21, 2018
A study conducted at The Wistar Institute in collaboration with The University of Texas Southwestern Medical Center has demonstrated the efficacy of targeting aberrantly active telomerase to treat therapy-resistant melanoma. ...

A small, daily dose of Viagra may reduce colorectal cancer risk

March 19, 2018
A small, daily dose of Viagra significantly reduces colorectal cancer risk in an animal model that is genetically predetermined to have the third leading cause of cancer death, scientists report.

Cancer comes back all jacked up on stem cells

March 19, 2018
After a biopsy or surgery, doctors often get a molecular snapshot of a patient's tumor. This snapshot is important - knowing the genetics that cause a cancer can help match a patient with a genetically-targeted treatment. ...

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...


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.