Study finds potential marker of drug response in many cancer types

February 21, 2017 by Allison Hydzik

Researchers at the University of Pittsburgh School of Medicine have uncovered a novel genetic mechanism of thyroid cancer, as well as a marker that may predict response to a particular class of drugs, not just in patients with thyroid cancer, but in those with many other types of cancer as well. The new findings were published in Proceedings of the National Academy of Science.

"These results further our understanding of the biology of . More broadly, they also suggest a potential treatment strategy for many different types of cancer," explained lead study author Yuri Nikiforov, M.D., Ph.D., professor of pathology, vice chair for molecular pathology and director of UPMC's Division of Molecular & Genomic Pathology.

Thyroid cancer is the fastest-growing type of cancer in the U.S., and more than 55,000 people will be newly diagnosed this year. Like many other cancers, thyroid tumors usually result from specific genetic abnormalities. Although previously identified mutations are found in about 90 percent of thyroid cancers, in the remaining cases the culprit is still a mystery.

To identify new associated with thyroid cancer, Nikiforov and his team applied a powerful technology called next-generation sequencing to analyze a series of papillary thyroid carcinomas (the most common form of thyroid cancer) that did not contain any of the known mutations.

The researchers found that a significant proportion of these tumors had a complex genetic alteration involving fusion of a gene named THADA to a previously unknown region near a gene called IGF2BP3. The result of this gene fusion was elevated levels of IGF2BP3 protein, an important component of the IGF1R protein signaling pathway that is known to play a role in tumor formation and growth.

"Up until now, we knew that alterations in the THADA gene were associated with thyroid cancer, but we didn't know how this genetic change actually leads to tumor development," explained Nikiforov. "Our study uncovers a new mechanism of thyroid cancer, one that is actually quite common."

The team went on to find that elevated IGF2BP3 also was present in many other types of cancer.

"When we looked at other common cancers, such as those of the lung, pancreas, colon and ovary, we found that 5 to 15 percent of them had elevated levels of IGF2BP3," said Nikiforov.

The team then performed cell culture and animal model experiments that revealed that growth of these tumors could be blocked by IGF1R pathway-inhibiting drugs.

A number of IGF1R inhibitors have been developed and tested in more than 25 clinical trials in the last several years, Nikiforov explained. Unfortunately, these trials failed because only a small subpopulation of patients responded to the drugs, and researchers were not able to determine which tumors would be susceptible to the treatment.

"Our results suggest that we now have a genetic marker – IGF2BP3 – that may be able to tell us who will benefit from these drugs," he said. "What's really exciting is that our study could renew interest in the use of IGF1R inhibitors to treat cancer. We hope that the manufacturers of IGF1R and IGF2 inhibitors will consider initiating for these drugs specifically in patients whose tumors show elevated levels of IGF2BP3."

Explore further: Clinical trial for genetic cancer test to offer safe thyroid-preserving surgery

More information: Federica Panebianco et al. fusion is a mechanism of IGF2BP3 activation and IGF1R signaling in thyroid cancer, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1614265114

Related Stories

Clinical trial for genetic cancer test to offer safe thyroid-preserving surgery

February 8, 2017
University of Pittsburgh School of Medicine scientists and doctors are embarking on the first-ever clinical trial to determine if a genetic test they pioneered could successfully spare patients with nonaggressive thyroid ...

International panel reclassifies thyroid tumor to curb overdiagnosis of cancer

April 14, 2016
Led by researchers at the University of Pittsburgh School of Medicine, an international panel of pathologists and clinicians has reclassified a type of thyroid cancer to reflect that it is noninvasive and has a low risk of ...

CVD, osteoporosis risk up for young thyroid cancer survivors

January 26, 2017
(HealthDay)—Younger survivors of thyroid cancer are at increased risk for certain types of health problems later in life, according to a study presented at the American Society of Clinical Oncology's Cancer Survivorship ...

BRAF addiction of thyroid cancers makes them therapeutically vulnerable

November 21, 2011
Papillary carcinoma is the most common form of thyroid cancer. Approximately one quarter of these carcinomas have mutations in the BRAF gene. The prevalence of such mutations is even greater in high-grade carcinomas, particularly ...

Next generation sequencing test improves detection of thyroid cancer, reduces unnecessary surgeries

October 1, 2013
A new test for genetic markers that can identify which lumps in the thyroid gland are cancerous and which are harmless – potentially preventing unneeded operations – will make its debut Oct. 1 for patients seeking care ...

The calling card of aggressive thyroid cancer

November 2, 2016
A new discovery from University of Alberta scientists represents an important milestone in the fight against thyroid cancer. In a study published in EBioMedicine and recently presented at the American Thyroid Association ...

Recommended for you

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

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.