Novel gene editing approach to cancer treatment shows promise in mice

May 1, 2017
cancer
Killer T cells surround a cancer cell. Credit: NIH

A novel gene therapy using CRISPR genome editing technology effectively targets cancer-causing "fusion genes" and improves survival in mouse models of aggressive liver and prostate cancers, University of Pittsburgh School of Medicine researchers report in a study published online today in Nature Biotechnology.

"This is the first time that gene editing has been used to specifically target . It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer," explained lead study author Jian-Hua Luo, M.D., Ph.D., professor of pathology at Pitt's School of Medicine and director of its High Throughput Genome Center.

Fusion genes, which often are associated with cancer, form when two previously separate genes become joined together and produce an abnormal protein that can cause or promote cancer.

Luo and his team had previously identified a panel of fusion genes responsible for recurrent and aggressive prostate cancer. In a study published earlier this year in the journal Gastroenterology, the team reported that one of these fusion genes, known as MAN2A1-FER, also is found in several other types of cancer, including that of the liver, lungs and ovaries, and is responsible for rapid tumor growth and invasiveness.

In the current study, the researchers employed the CRISPR-Cas9 genome editing technology to target unique DNA sequences formed because of the . The team used viruses to deliver the tools that cut out the mutated DNA of the fusion gene and replaced it with a gene that leads to death of the . Because the fusion gene is present only in cancer cells, not healthy ones, the gene therapy is highly specific. Such an approach could come with significantly fewer side effects when translated to the clinic, which is a major concern with other cancer treatments such as chemotherapy.

To conduct the study, the researchers used mouse models that had received transplants of human prostate and liver cancer cells. Editing the cancer fusion gene resulted in up to 30 percent reduction in tumor size. None of the mice exhibited metastasis and all survived during the eight-week observation period. In contrast, in control mice treated with viruses designed to cut out another not present in their tumors, the tumors increased nearly 40-fold in size, metastasis was observed in most animals, and all died before the end of the study.

The new findings suggest a completely new way to combat cancer. "Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy's soldiers to regroup in the battlefield for a comeback," said Luo.

Another advantage over traditional cancer treatment is that the new approach is very adaptive. A common problem that renders standard chemotherapies ineffective is that the cancer cells evolve to generate new mutations. Using genome editing, the new mutations could be targeted to continue fighting the disease, Luo noted.

In the future, the researchers plan to test whether this strategy could completely eradicate the disease rather than induce the partial remission observed in the current study.

Explore further: A new approach to target an 'undruggable' prostate cancer driver

More information: Targeting genomic rearrangements in tumor cells through Cas9-mediated insertion of a suicide gene, Nature Biotechnology (2017). nature.com/articles/doi:10.1038/nbt.3843

Related Stories

A new approach to target an 'undruggable' prostate cancer driver

March 23, 2017
New research suggests a novel strategy to target a genetic anomaly that occurs in half of all prostate cancers.

New model could speed up colon cancer research

May 1, 2017
Using the gene-editing system known as CRISPR, MIT researchers have shown in mice that they can generate colon tumors that very closely resemble human tumors. This advance should help scientists learn more about how the disease ...

CAR T cells more powerful when built with CRISPR, researchers find

February 22, 2017
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have harnessed the power of CRISPR/Cas9 to create more-potent chimeric antigen receptor (CAR) T cells that enhance tumor rejection in mice. The unexpected findings, ...

Skin cancer causing fusion gene identified

November 1, 2015
Angiosarcoma is a malignant cancer of the endothelial cells of blood or lymphatic vessels. Cutaneous angiosarcoma, a form of skin cancer, commonly occurs on the scalp of elderly people and can rapidly metastasize to the liver, ...

Predicting prostate cancer: Test identifies new methods for treatment

September 15, 2014
A genetic discovery out of the University of Pittsburgh School of Medicine is leading to a highly accurate test for aggressive prostate cancer and identifies new avenues for treatment.

Recommended for you

Researchers drill down into gene behind frontotemporal lobar degeneration

October 19, 2017
Seven years ago, Penn Medicine researchers showed that mutations in the TMEM106B gene significantly increased a person's risk of frontotemporal lobar degeneration (FTLD), the second most common cause of dementia in those ...

New clues to treat Alagille syndrome from zebrafish

October 18, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies potential new therapeutic avenues for patients with Alagille syndrome. The discovery, published in Nature Communications, ...

Genetic variants associated with obsessive-compulsive disorder identified

October 18, 2017
(Medical Xpress)—An international team of researchers has found evidence of four genes that can be linked to obsessive-compulsive disorder (OCD). In their paper published in the journal Nature Communications, the group ...

An architect gene is involved in the assimilation of breast milk

October 17, 2017
A family of "architect" genes called Hox coordinates the formation of organs and limbs during embryonic life. Geneticists from the University of Geneva (UNIGE) and the Swiss Federal Institute of Technology in Lausanne (EPFL), ...

Study identifies genes responsible for diversity of human skin colors

October 12, 2017
Human populations feature a broad palette of skin tones. But until now, few genes have been shown to contribute to normal variation in skin color, and these had primarily been discovered through studies of European populations.

Genes critical for hearing identified

October 12, 2017
Fifty-two previously unidentified genes that are critical for hearing have been found by testing over 3,000 mouse genes. The newly discovered genes will provide insights into the causes of hearing loss in humans, say scientists ...

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.