New Research Aims To Develop Targeted Therapy For Hard-to-treat Osteosarcoma

For children and young adults diagnosed pinch osteosarcoma, a communal type of bony crab for that property group, nan likelihood of endurance tin beryllium devastatingly debased (20-30%) erstwhile nan illness spreads to nan lungs.

Treatments for osteosarcoma haven't changed since nan 1980s. That leaves america pinch a captious request for much effective and innovative therapies for these patients."

Balakrishna Koneru, Ph.D.

In an effort to amended nan outcomes for these young patients, nan Cancer Prevention and Research Institute of Texas (CPRIT) precocious awarded a two-year, $198,822 assistance to Koneru, an assistant professor of pediatrics astatine TTUHSC's School of Medicine and Graduate School of Biomedical Sciences, and a erstwhile postdoctoral interrogator for C. Patrick Reynolds, M.D., Ph.D., head of nan TTUHSC School of Medicine Pediatric Cancer Research Center.

The assistance ("Investigating Integrin Subunit Alpha-V arsenic a Therapeutic Target successful ALT-Dependent Osteosarcomas") is simply a CPRIT Texas Regional Excellence successful Cancer: Pilot Study Award. These awards supply up to $200,000 complete 2 years to investigators who are conducting original and innovative crab research, located successful Texas regions historically underserved by crab investigation and moving 100 miles aliases much from a National Cancer Institute-designated crab halfway located wrong nan state.

Koneru said osteosarcomas are 1 of respective cancers that often person mediocre outcomes because their cells usage a typical endurance instrumentality called replacement lengthening of telomeres aliases ALT. Telomeres are caps connected nan extremity of chromosomes that protect nan familial accusation contained wrong nan cell. Cancer cells request to support lengthening these telomeres to continuing dividing. 

"Most cancers do this by turning connected an enzyme called telomerase, but immoderate alternatively move connected ALT," Koneru explained. "ALT is particularly communal successful definite sarcomas and successful fierce forms of puerility neuroblastoma. Unfortunately, cancers that trust connected ALT are very difficult to treat, and location are presently nary therapies designed to specifically target them."

Koneru said his group antecedently has shown that astir 70% of osteosarcoma patients person tumors driven by ALT, a telomere attraction system that tin beryllium detected pinch a reliable laboratory test. Because osteosarcoma shows specified a precocious prevalence of nan ALT phenotype, his investigation has focused connected this crab type.

Using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) screenings, which make it imaginable to change thousands of genes astatine erstwhile to place those basal for tumor survival, nan squad discovered that a macromolecule called Integrin Alpha V (ITGAV) plays a captious domiciled successful nan endurance of ALT-driven osteosarcomas.

"This connection is focused connected investigating ITGAV arsenic a imaginable therapeutic target for these difficult-to-treat tumors," Koneru added.

Supported by this CPRIT grant, Koneru's laboratory will activity to grow connected its caller activity pinch ITGAV to fortify its findings and show nan protein's value successful treating ALT-driven cancers. If successful, he said nan study could pave nan measurement for a caller supplier to treat osteosarcoma. 

"The ITGAV gene is basal for ALT-positive osteosarcomas," Koneru said. "In this study, we are trying to fig retired precisely why it's basal and if we tin create this arsenic a therapeutic target for ALT-dependent osteosarcoma."

Depending connected nan study's outcome, Koneru said their findings besides could beryllium expanded to different cancers.

"It's not conscionable osteosarcoma, but different sarcomas which besides are known to person a precocious prevalence of ALT," Koneru said. "They besides tin perchance beryllium targeted utilizing a circumstantial supplier that we mightiness find during our research."