New bowel cancer drug target discovered

October 17, 2017, The Francis Crick Institute
Credit: CC0 Public Domain

Researchers at the Francis Crick Institute have discovered a new drug target for bowel cancer that is specific to tumour cells and therefore less toxic than conventional therapies.

"There has long been a need to find more effective and less toxic drugs to treat ," says Laura Novellasdemunt, first author of the paper and researcher at the Francis Crick Institute. "We have found a novel that could provide the basis for a better therapy in patients in the future."

Most bowel cancers are caused by a mutation in a gene called APC that in its healthy form acts to prevent cancer formation. Mutated APC genes cause excess activity of a cell signalling pathway called 'Wnt', which has been associated with bowel cancer for over 20 years.

Wnt signalling is vital for many organs, so drugs designed to block Wnt signalling in cancer cause very toxic side effects in other parts of the body. This has been a major hurdle in developing effective and safe bowel cancer therapies. The team at the Crick have found a way to exclusively target Wnt signalling in , that reduces growth of tumours derived from without the toxic effects on . Their findings will be published in Cell Reports.

The team used the gene-editing tool CRISPR to cut the APC gene at various positions, and found a crucial part of the gene that causes dangerous levels of Wnt signalling and cancer formation.

Using a number of molecular techniques, they identified a protein involved in over activation of the Wnt pathway in cancer. Preventing the activity of this protein by genetic deletion or blocking it with drugs caused a reduction in Wnt signalling in cancer cells and slowed down tumour growth in mice. Importantly, the drug was found to act exclusively on the tumour cells, and have no effect on Wnt signalling in healthy cells.

"Current treatment for bowel cancer is mostly generic, while targeted therapy will help future development of personalised medicine," says Vivian Li, senior author of the paper and Group Leader at the Francis Crick Institute. "The protein that we've identified holds great promise as a therapeutic target for bowel cancer treatment."

The next step will be to see if deleting the gene that makes the protein in mice will prevent them from developing bowel cancer. This will provide further evidence that the protein is a viable anti-cancer drug target.

Explore further: New strategy against childhood cancer

More information: 'USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating β-catenin deubiquitination' Cell Reports (2017). DOI: 10.1016/j.celrep.2017.09.072 , http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31377-3

Related Stories

New strategy against childhood cancer

July 27, 2017
Neuroblastoma is a cancer in children that originates in the sympathetic nervous system and has a high mortality. Current treatment includes chemotherapy and radiotherapy with their potentially severe side effects; there ...

Active hedgehog signalling in connective tissue cells protects against colon cancer

August 8, 2016
Many types of cancer are caused by gene mutations in the signalling pathways that control cell growth, such as the hedgehog signalling pathway. A new study from the Karolinska Institutet, published in the journal Nature Communications, ...

Scientists discover why bowel cancer sometimes outsmarts treatment

December 1, 2014
A new study that challenges the prevailing view of how bowel cancer develops in the large intestine is published today in Nature Medicine.

Bowel cancer study reveals impact of mutations on protein networks

August 29, 2017
For the first time, scientists have completed a detailed study of many of the proteins in bowel cancer cells. Scientists from the Wellcome Trust Sanger Institute investigated the role proteins play in predicting how common ...

Scientists discover how iron levels and a faulty gene cause bowel cancer

August 9, 2012
High levels of iron could raise the risk of bowel cancer by switching on a key pathway in people with faults in a critical anti-cancer gene, according to a study published in Cell Reports today.

Researchers reveal how cancer cells cope with genetic chaos

January 9, 2017
Scientists have uncovered how tumours are able to grow despite significant damage to the structure and number of their chromosomes - the storage units of DNA - according to two new studies published in Cancer Cell and Cancer ...

Recommended for you

What can salad dressing tell us about cancer? Think oil and vinegar

September 20, 2018
Researchers led by St. Jude Children's Research Hospital scientists have identified another way the process that causes oil to form droplets in water may contribute to solid tumors, such as prostate and breast cancer. The ...

Novel biomarker found in ovarian cancer patients can predict response to therapy

September 20, 2018
Despite months of aggressive treatment involving surgery and chemotherapy, about 85 percent of women with high-grade wide-spread ovarian cancer will have a recurrence of their disease. This leads to further treatment, but ...

Testing fluorescent tracers used to help surgeons determine edges of breast cancer tumors

September 20, 2018
A team of researchers with members from institutions in The Netherlands and China has conducted a test of fluorescent tracers meant to aid surgeons performing tumor removal in breast cancer patients. In their paper published ...

Cancer immunotherapy might benefit from previously overlooked immune players

September 20, 2018
Cancer immunotherapy—efforts to boost a patient's own immune system, allowing it to better fight cancer cells on its own—has shown great promise for some previously intractable cancers. Yet immunotherapy doesn't work ...

New way to target advanced breast cancers

September 20, 2018
A cytokine signature found in certain kinds of breast cancer cells can not only serve as a diagnostic tool for HER2-negative cancers but also offer an effective treatment target.

Understanding epilepsy in pediatric tumors

September 20, 2018
Pediatric brain tumors are characterized by frequent complications due to intractable epilepsy compared to adult brain tumors. However, the genetic cause of refractory epilepsy in pediatric brain cancer has not been elucidated ...

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.