More than 50 posters were submitted for judging at the fifth annual Dr. Gary Kruh Research Symposium and Poster Competition, and the studies explored all avenues of cancer research, from the role PAX8 plays in modulating the tumor microenvironment of high-grade serous ovarian cancer to single-cell 3D spatial multiomics to access tumor heterogeneity.
University of Illinois Cancer Center members and patient advocates voted on the posters, and seven winners (two from each of the Cancer Center research programs; a tie for second place was reached in the Translational Oncology program) walked away with $500 each for their work. Without further ado, the winners are…
Roles of chromatin higher-order many-body units of 3D interactions in concurrent regulation of multiple genes: A study of eQTL loci
Presenter: Hammad Farooq
Mentor: Jie Liang, PhD, Richard and Loan Hill Department of Bioengineering
Chromatin folding plays important roles in the regulation of gene expression, which control cellular activities and are the basis of differentiation. With long-range spatial chromatin interactions, functional elements far away from the target gene contribute to gene regulation. Variants at these functional elements can therefore affect gene expression. While there is a large amount of data on eQTLs, which are variants that are linked to gene expression, how distal variants modulate gene expression are not well understood. Read more in Box.
Investigating the role of PAX8 in modulating the tumor microenvironment of high-grade serous ovarian cancer
Presenter: Amrita Salvie
Mentor: Joanna Burdette, PhD, Department of Pharmaceutical Sciences
High grade serous ovarian cancer (HGSC), the most common and lethal form of ovarian cancer, is a highly heterogeneous disease. HGSC is rarely detected early, and likely arises from the fimbriated end of the fallopian tube epithelium (FTE), and in some cases, the ovarian surface epithelium (OSE).
PAX8 is a commonly used biomarker for ovarian serous tumors and is expressed in ~80-96% of HGSC. Although the OSE does not express PAX8, murine models of HGSC derived from the OSE acquire PAX8, suggesting that it is not only a marker of Müllerian origin, but also an essential part of cancer progression, potentially from both the OSE and FTE. Our data indicates that PAX8 loss by CRISPR and shRNA in HGSC cell lines causes tumor cell death and reduces cell migration and invasion. Additionally, loss of PAX8 appears to play an important role in the production of matrix in the tumor that contributes to tumor stiffness, poor outcomes, and hinders immune cell invasion. We have performed secretome analysis of PAX8 deleted cells and found a reduction of extracellular matrix (ECM) components collagen and fibronectin. This finding was validated by immunoblotting and immunofluorescence in PAX8 deleted HGSC cells. Read more in Box.
Cancer Prevention and Control
Primary Care Providers’ Knowledge of Hereditary Cancer Syndromes and Confidence with the Use of Cancer Genetic Services at Federally Qualified Health Centers
Presenter: Sarah Stettner
Mentor: Deborah Manst, MD, MPH, University of Illinois Cancer Center – Cancer Prevention & Survivorship
Background: Underutilization of cancer genetic services leads to missed opportunities to provide early intervention for patients with hereditary cancer syndromes. Common barriers to referral include patient refusal, cost concerns, and lack of knowledge about genetics services or recommendations.
Minority and underserved patients are known to have especially limited access to cancer genetic services, but the knowledge of barriers specifically within Federally Qualified Health Centers (FQHCs) is limited. The goal of this study was to gather feedback from Primary Care Providers (PCPs) at FQHCs on hereditary cancer syndromes and cancer genetic referrals to work towards increasing access and health equity. Read more in Box.
Terminology Used by Patients & Clinicians to Refer to Trastuzumab Biosimilars
Presenter: Devika Salunke
Mentor: Elizabeth Lerner Papautsky, PhD, Department of Biomedical & Health Information Services
Background: Biosimilars have the potential to reduce treatment costs at an institutional level; however, they are relatively new to the American markets, and the information surrounding them can be highly technical and complex. Literature suggests that healthcare professionals who have previously prescribed biosimilars also have a limited understanding of this category of drugs (Yang et al., 2021a; Yang et al., 2021b)(1).
Due to the complexity of the subject, there may be limited development of colloquial vocabulary around biosimilars resulting in limited dissemination of information to the general public. Research suggests that a lack of shared language and knowledge between patients and their healthcare providers affects communication and information exchange between the two parties (Kuziemsky & Varpio, 2010). (2). This can potentially affect the adoption and acceptance rate of biosimilars. Here we use a qualitative approach to document the self-reported language used by healthcare providers and patients to describe Trastuzumab biosimilars. Read more in Box.
Single-Cell 3D Spatial MultiOmics (sc3DSMO) to Access Tumor Heterogeneity
Presenter: Yi-Chien Wu
Mentor: Steve Seung-Young Lee, PhD, Department of Pharmaceutical Sciences, College of Pharmacy
For many years, cancer has been the leading cause of death in the world. A major challenge to successful cancer treatment is intra-tumor heterogeneity. Diverse tumor cell populations within a tumor result in uneven treatment efficacy, giving rise to resistant tumor cell clones. As such, tumor heterogeneity plays an indispensable role in poor treatment outcomes and cancer relapse.
Two critical factors, intrinsic genetic differences among tumor cells and their spatial locations in the tumor microenvironment, constantly influence cell functions, phenotypes, and tumor heterogeneity. Therefore, to obtain a comprehensive understanding of tumor heterogeneity, it is necessary to detect single-tumor-cell variation and reveal the location information of cells. In the past several years, the advent of spatial omics technologies offers a revolutionized way to characterize cells at a systematic level while retaining the spatial information of molecular expression. Commercialized spatial transcriptomic technology, 10x Genomics Visium platform, and spatial proteomics technology, Nanostring’s GeoMx digital spatial profiler (DSP), offer streamlined omics analyses and are widely applied to many tumor types. However, the restrictions of being low capture sensitivity, limited analytical area, and thin tissue sample requirement (10-μm thick) hinder the application of Visium in 3D tumor investigation. Read more in Box.
Second Place – Tie
Increased Utilization of Stereotactic Body Radiotherapy Has Decreased Disparities for Early-Stage NSCLC
Presenter: Ashwin Ganesh
Mentor: Matthew Koshy, MD, College of Medicine
Introduction: Previous research has shown significant treatment disparities for Black patients who are less likely to receive curative therapy for early-stage lung cancer. We sought to determine if increased use of stereotactic body radiation therapy (SBRT) has led to an increase in the proportion of patients receiving definitive treatment for early-stage non-small cell lung cancer (NSCLC).
Methods: The National Cancer Database (NCDB) was utilized to determine the proportion of patients with NSCLC receiving surgical treatment, SBRT, or no definitive treatment (observation) for clinical stage T1-T2 N0M0 NSCLC from 2004 to 2017. The receipt of treatment for NSCLC was evaluated in terms of the overall population and by race. A two-sample t-test was used to compare continuous variables. Univariable and multivariable logistic regressions were used to determine factors associated with the likelihood of receiving definitive treatment. Variables were included in the multivariable analysis (MVA) if they were found to be associated with receiving treatment (p<0.1) on univariable analysis (UVA). Read more in Box.
Second Place – Tie
Overcoming drug resistance to G12C inhibitors in patient-derived organoids with a multiarray platform
Presenter: Endrino Pulido
Mentor: Takeshi Shimamura, PhD, MS, Department of Surgery, College of Medicine
KRAS is the most frequently mutated oncogene driver in cancer and is particularly common in lung, pancreatic and colorectal cancers. While KRAS mutants haven’t been considered to be undruggable, covalent G12C inhibitors, sotorasib and adagrasib, that bind preferentially to GDP-bound KRAS and prevent the exchange for GTP and the interaction with its effectors have been approved for the use in NSCLC and earned FDA-accelerated status, respectively.
While these reagents show promising efficacy and are well tolerated by patients, acquired drug resistance to sotorasib occurs rather quickly; thus, novel approaches that either delay or overcome sotorasib resistance will be needed. While established NSCLC cell lines offer utilities in delineating the acquired resistance to these inhibitors, very few work has utilized Patient Derived Organoids (PDOs), which maintain tumor architecture and provide drug responses like NSCLC patients to investigate the mechanisms of acquired KRAS G12C inhibitor resistance. Read more in Box.