Ongoing research by the Cole Lab has shown that pediatric cancers rely upon a cell's normal repair mechanisms to overcome the cellular stress that results from continued growth caused by cellular mutations and oncogenic stimuli, particularly by the MYC and MYCN oncogenes. Among these repair genes are signaling mediated by the CHK1, ATR and Wee1 kinases, which when inhibited halt cancer cell growth. From this work, a clinical trial is currently underway to evaluate the safety and efficacy of combining a Wee1 inhibitor and chemotherapy as treatment for relapsed neuroblastoma and medulloblastoma.
Other research in the laboratory involves identifying the proteins required for malignant gliomas with alternative lengthening of telomeres (ALT) to continue to proliferate. To do these studies the Cole laboratory is performing high-throughput screening of patient-derived cell lines from tumors of children with malignant glioma with and without ALT in collaboration with the multi-institution Children's Brain Tumor Tissue Consortium.
The Cole Laboratory is also interested in understanding how the non-coding genome is involved in pediatric cancer development and progression. In collaboration with members of the Maris Lab, the Cole Lab discovered both short (miR-34a) and long (CASC15) noncoding RNAs that contribute to neuroblastoma tumorigenesis. In the future, Kristina Cole, MD, PhD, and her laboratory team hope to identify treatments that will improve the survival of children with malignant brain tumors.
- Clinical translation of molecular targets: The Cole Lab has performed loss of function genetic screens supporting four pediatric oncology clinical trials. The lab developed and leads a Children's Oncology Group multi-institution clinical trial of the Wee1 inhibitor Adavosertib /AZD1775 and Irinotecan (ADVL1312). The Phase I dose finding portion is complete and the Phase II portion of the study is currently accruing patients to determine the clinical activity for children with relapsed neuroblastoma, medulloblastoma and rhabdomyosarcoma.
- Single cell analysis of pediatric solid tumors: The lab is contributing its expertise in molecular pathology and pediatric cancer genomics by performing temporal and spatial multi-omic single cell analyses from prospectively collected pediatric neuroblastoma, malignant glioma and high-risk leukemia patient specimens.Study of pediatric high-grade glioma with ATRX deficiency / ALT: Since about a third of those with high-grade glioma have ATRX deficiency and alternative lengthening of telomeres (ALT), the Cole Lab's efforts have focused on targeting these vulnerabilities. In collaboration with the Childrens Brain Tumor Tissue Consortium, the lab has created reagents to accomplish this, including an integrated set of 70 sequenced tumors with corresponding cell lines, patient derived xenografts and a tissue microarray.
Dr. Cole is a pediatric neuro-oncologist who has dedicated her career to translational and clinical research, combining her expertise in molecular pathology, cancer genomics, and developmental therapeutics to identify novel treatments for children with cancer.