Co-Leader: David Carbone, MD, PhD
Co-Leader: Elaine Mardis, PhD
Co-Leader: Blake Peterson, PhD
The overall goal of the newly developed Translational Therapeutics (TT) Program at the Ohio State University Comprehensive Cancer Center (OSUCCC) is to pursue solid tumor biology in order to develop and translate promising preclinical studies into innovative clinical trials for the successful prevention, diagnosis and treatment of solid tumors. The TT Program is focused on molecular targeting, biomarker development and understanding the human immune response in human solid tumors.
TT Cancer Focus
About TT Members
Dr. Carbone has internationally acclaimed expertise in lung cancer. Dr. Carbone’s group is now building upon their experience in the immune-based therapy of NSCLC and identifying novel strategies to combine checkpoint inhibitors with each other and with other therapies in the treatment of NSCLC. Specifically, he is leading a national, multi-institutional study of neoadjuvant immunotherapy in surgically resectable NSCLC with comprehensive biomarker analyses in order to better understand the basis of response and non-response to checkpoint blockade (NCT02927301).
TT members include 79 basic, translational and/or clinical researchers from 18 departments within the Colleges of Medicine, Pharmacy, Public Health and Veterinary Medicine at The Ohio State University. Full members of the TT Program are funded cancer investigators whose work is focused on translation as defined in the aims. Also included are clinical investigators who conceive, design and conduct peer-reviewed human clinical trials.
The TT Program produced 1199 publications of 19% are intra-programmatic collaborations, 34% are inter-programmatic collaborations and 77% are multi-institutional publications, with 88% total collaborative publications.
Key Program Objectives
Identify alterations in solid tumor signaling pathways to develop targeted therapeutics.
Research in this aim is focused on the elucidation of alterations in cell signal transduction, proliferative and survival pathways that promote tumorigenesis in the malignant cell and the development of therapeutic strategies to reverse or counteract these alterations.
Identify and therapeutically target tumor-host interactions, including immuno-oncology.
The goals of this aim are to first understand the tumor-host interaction within the tumor microenvironment (TME) as well as the tumor’s ability to evade the immune system. The second goal is to explore methods that favorably alter the TME for activation of host immune effector cells and/or reversal of the tumor’s ability to suppress the anti-tumor response.
Improve upon or develop new approaches for determining prognosis, selecting appropriate therapy and evaluating the response to treatment.
The object of research conducted under this aim is to characterize tumors at the genomic, molecular, cellular and tissue levels and utilize this information to guide prognostic and therapeutic decision-making for the purpose of improving clinical outcomes.
Controllable Self-Assembly of RNA Tetrahedrons With Precise Shape and Size for Cancer Targeting. RNA tetrahedral nanoparticles with two different sizes are successfully assembled by a one-pot bottom-up approach with high efficiency and thermal stability. The reported design principles can be extended to construct higher-order polyhedral RNA architectures for various applications such as targeted cancer imaging and therapy. Published in Advanced Materials.
PI: Peixuan Guo, PhD
Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Published in Cancer Research.
PIs: O. Hans Iwenofu, MBBS; James Chen, MD; Carlo Croce, MD; Raphael Pollock, MD, PhD
A Transcriptional Signature Identifies LKB1 Functional Status as a Novel Determinant of MEK Sensitivity in Lung Adenocarcinoma. LKB1 is a commonly mutated tumor suppressor in non-small cell lung cancer that exerts complex effects on signal transduction and transcriptional regulation. To better understand the downstream impact of loss of functional LKB1, we developed a transcriptional fingerprint assay representing this phenotype. Published in Clinical Cancer Research.
PIs: David Carbone, MD, PhD
IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells. Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status. Published in Clinical Cancer Research.
PIs: Susheela Tridandapani, PhD; Terence Williams, MD, PhD; William Carson, MD
First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. Published in New England Journal of Medicine.
PI: David Carbone, MD, PhD;
The following are some of the future key areas of focus for the TT Program:
- Host-tumor interactions
- Biomarkers relevant to immunotherapy
- Development of the new Pelotonia Institute for Immune-Oncology