Researchers from the Case Comprehensive Cancer Center have discovered how unusually long strands of RNA help colon cancer cells avoid death, allowing unregulated growth. Unlike other RNAs, the intriguing strands do not appear to encode proteins and are termed "long non-coding RNAs" or "lincRNAs." A new study showed some lincRNAs could be targeted by drug developers to halt colon cancer.

In a new study published in  Scientific Reports [Forrest, Sci Reports, 2018], researchers compared lincRNA levels inside tumor cells, to levels inside healthy colon cells. They found over 200 lincRNAs at significantly different levels inside the tumor cells as compared to normal cells. One in particular, called lincDUSP, was overexpressed in 91 percent of the tumor samples. A few tumors had more than fifteen times the normal amount of lincDUSP. The significant increase suggested this mysterious, and previously uncharacterized, RNA could be cancer-causing. 

"Our work demonstrates that not only protein-coding genes but also non-coding genes contribute to colon cancer progression," says Ahmad Khalil, PhD, senior author, assistant professor of genetics and genome sciences at Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. "LincRNAs could be exploited as direct drug targets in this and other human diseases."

Co-authors on this study include Megan E. Forrest, Alina Saiakhova, Lydia Beard, David A. Buchner, Peter C. Scacheri, Thomas LaFramboise, and Sanford Markowitz. This research was partially supported by the Case Comprehensive Cancer Center Integrated Genomics Shared Resource and Cytometry and Microscopy Shared Resource.  more>

Cleveland Clinic researchers have demonstrated for the first time that lowering blood cholesterol levels could enhance the success of a specific type of T-cell immunotherapy in fighting cancer [ Ma, J Exp Med, 2018].

The team, led by  Qing Yi, MD, PhD of the Cleveland Clinic and Case Comprehensive Cancer Center, studied T-cell transfer, which has shown great success in recent years. Dr. Yi previously showed that a specific subset of T-cells, called Tc9 cells, have stronger anti-tumor effects than other types of T-cells. In the new study, they determined the mechanisms that give Tc9 cells their anti-cancer properties and how these mechanisms might be tweaked to enhance immunotherapy. 

Using gene profiling, the researchers discovered that Tc9 cells had much lower levels of intracellular cholesterol than other T-cells. They hypothesized that the reduced cholesterol levels might contribute to the cells' anti-tumor effects. Indeed, when cholesterol-lowering drugs were administered to the cells, anti-cancer pathways were turned on (IL-9 expression and NF-KB signaling). Furthermore, they showed in a tumor-bearing preclinical model that reducing cholesterol levels prior to immunotherapy led to greater concentrations of IL-9 and better cancer-killing success.  more>

Jun 4, 2018, 5-7p  | Wolstein Research Bldg

Join us for the next Cancer Center Scientific Series and hear updates from recipients of VeloSano pilot awards. Presentations will be followed by a reception. 

Mark Jackson, PhD

A high-throughput screen for inhibitors of cancer stem cell plasticity

Julian Kim, MD

Development of intravenously injectable β-glucan treatment for regulating granulocytic myeloid-derived suppressive cells

Shigemi Matsuyama, PhD

Development of new type of therapeutics selectively targeting Bax or Bak

Alvin Schmaier, MD

Tyrosine kinase inhibitors and cardiovascular events in CML

Andrew Sloan, MD
Hematologic biomarkers of treatment response & recurrence in patients with glioblastoma

Zhenghe John Wang, PhD

Develop GPT2 inhibitors to target PI3KCA-mutated colorectal cancers 

Youwei Zhang, PhD

Roles of UbcH7 in tumorigenesis and therapy response 

Researchers are looking for 120,000 women nationwide to take part in a study that might lead to detecting cancer with a blood test  The Cleveland Clinic is teaming up with the Mayo Clinic, as well as several other hospitals across the country, for the STRIVE study. It's a study that will use advanced technology to look for small pieces of genetic material released into the blood by tumors..."This goes beyond breast cancer," said Dr. Stephen Grobmyer, Case Comprehensive Cancer Center, Director of the Breast Center at the Cleveland Clinic. "This would be a way to screen for not only breast cancer but other cancers with a blood test."

Deadline: Aug 1, 2018