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8 Clinical OMICs July/August 2017 www.clinicalomics.com News For patients suffering from pain, opioids often provide much-needed relief. On the other hand, opioid over- dose is a major problem, particularly in the United States, where, accord- ing to the Centers for Disease Control and Prevention, deaths from overdose have quadrupled since 1999. "Having pain can be very traumatic, but [receiving] too much pain medi- cation, like opioids, is also very dan- gerous," said Ron van Schaik, Ph.D., a professor of pharmacogenetics at the Erasmus University Medical Center in Rotterdam, The Netherlands. "It's very important to have markers that can tell if someone needs more or less pain medication." However, he added, due to the wide variety of individual responses to these drugs, it can often be difficult for physicians to identify the ideal dose for a patient. To try to pinpoint genes that could help tailor pain treatment, Dr. van Schaik and his colleagues conducted a literature review of 4,257 studies of opioid genetics, which appeared in June in Clinical Chemistry. Through this analysis, the researchers identified 10 genes with the highest potential for clinical use. These included those encoding a member of the cytochrome P450 family, CYP2D6; a variant of an opioid receptor, OPRM1; and cate- chol-O-methyltransferase, COMT. After pinpointing these promising genetic targets, the team performed a number of follow-up investigations to further elucidate their effects, both on cancer patients at the Erasmus MC Cancer Institute, and in children at Sophia's Children's Hospital in Rot- terdam. One of these studies revealed children with distinctive genetic vari- ants of COMT and OPRM1—or a spe- cific combination of mutations—had different levels of pain sensitivity. Based on these results, the team also developed a "pain panel" for four of these genes, including OPRM1 and COMT, that clinicians can use if they suspect their patient might have a variant that causes altered sensitivity to opioid medications. While these genetic markers show promise for clinical use, more work is needed to tease the role of genes apart from other influences, such as the variety in patient illnesses—including cancer—and differences in individual susceptibility to pain. "In the clinical setting, we realized that indeed, genetics is a factor that can be taken into consideration, yet we also saw that there are many other fac- tors involved as well," Dr. van Schaik said. "There is a strong genetic com- ponent in there, but you still need to [look] more closely to see how you [could] base doses on those genetics." —Diana Kwon genetic mutation—specifically, particu- lar growth-factor-signaling genes—may benefit from IGF1R inhibitors. In the study, investigators analyzed the genome of 112 childhood and adult tumors. Scientists looked for mutations in the tumors to understand the mecha- nism of osteosarcoma development. The genetic information revealed a specific process for rearranging the chromosomes that results in several cancer-driving mu- tations at once. In 10% of the cases, the team discov- ered cancer-causing mutations in insulin- like growth factor (IGF)–signaling genes. IGF signaling plays a major role in bone growth and development during puberty. Researchers believe that IGF signaling is also implicated in the uncontrolled bone growth that is characteristic of osteosar- coma development. Past clinical trials of IGF1R inhibitors as a treatment for osteosarcoma yield- ed mixed results, although occasionally patients responded to therapy. IGF1R inhibitors have not been further tested in osteosarcoma, as it had been unclear which patients would benefit from the treatment. The current treatment for osteosarco- ma is chemotherapy followed by surgery, where the bone tumors are removed. There has not been a new treatment for osteosarcoma in almost 40 years. n (continued from page 6) Genetic Markers Could Aid Appropriate Dosing of Opioids BackyardProduction / Getty Images Mayo Clinic