Newswise — COLUMBUS, Ohio – New smart-drug treatment options for pancreatic cancer, immuno-oncology treatments and real-time immune-monitoring strategies are among the research topics to be presented by investigators at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) at the American Association for Cancer Research (AACR) annual meeting held April 14-19 at the Orange County Convention Center in Orlando, Florida.

A focal point for the cancer research community, the AACR annual meeting highlights the strongest cancer research from institutions around the world. Highlights from the OSUCCC – James team include:

TARGETED THERAPIES | PRECISION CANCER MEDICINE
A-1888: Clinical impact of FGFR inhibitors on FGFR2+ pancreatic cancer
This abstract describes the durable clinical outcomes of four FGFR2 fusion+ pancreatic cancer patients treated with FGFR-inhibitor drugs as well as pancreatic-specific analysis of FGFR alterations. The retrospective analysis of these tumors provides clinical evidence that there is a subpopulation of KRAS wild-type FGFR2 fusion+ pancreatic cancer patients who can have beneficial and lasting responses to FGFR-inhibitor drugs, suggesting a need to investigate and expand the availability of FGFR inhibitors to more cancer types.

  • Expert: Leah Stein (biomedical sciences PhD candidate)/Sameek Roychowdhury, MD, PhD, medical oncologist and scientist with the OSUCCC – James
  • Details: Poster Section 44, Monday, April 17, 1:30-5 p.m.

CANCER SURVIVORSHIP
A-6296: Prevalence and cancer-specific patterns of cannabis use among U.S. cancer survivors
Studies have suggested that cannabis has therapeutic potential for alleviating various cancer and treatment-related symptoms, such as cancer-related pain, chemotherapy-induced nausea and insomnia. Less is known about the prevalence and specific motivation to use cannabis among cancer survivors. This abstract describes a cross-sectional analysis of U.S. cancer survivors age 20 or older from the Behavioral Risk Factor Surveillance Survey (2016-2021), which included 96,594 cancer survivors. Researchers looked at frequency of use, reasons for use (medical vs. non-medical), demographic information and state legality status. Survivors who were young, male, not married, current smokers and drinkers, of low income, poor health status and with cancer-related pain were more likely to report using cannabis than their counterparts. Among cannabis users, females, non-smokers, non-drinkers and those with higher education levels, higher body mass index (BMI) and health conditions were more likely to use cannabis for medical reasons. By type, testicle, brain and cervix cancer survivors had the highest rates of use. Generally, use was substantially higher in states where cannabis is legal.

  • Expert: Ce Shang, PhD, Scientist with the OSUCCC – James Cancer Control Research Program
  • Details: Poster Section 27, Sunday, April 16, 1:30-5 p.m.

A-6889: New analysis tool for assessing complex biomarkers and immune activity in tumor micro-environment through lens of a single cell
To thoroughly harness the potential of immunotherapies for larger segments of patients, researchers must be able to evaluate multiple biomarkers at once and understand their spatial and functional relationships within the tumor-immune microenvironment. The standard technique allows for the evaluation of only one or two biomarkers at a time. This abstract describes a toolkit for combining the power of complex imaging technology that can simultaneously label up to six biomarkers in the same tissue slice with novel computational tools that help sift and sort data to help capture and understand spatial relationships both qualitatively and quantitatively. These computational spatial analyses tools for multiplexed imaging datasets are designed to extract information about tissue behavior (such as cell types, functional status, and how similar or dissimilar the cells look) and knowledge about how these cells are interacting with different cell types in different cases (such as before and after cancer treatment) can help researchers better understand the impact of immune-based treatments and, ultimately, design treatment regimens for different subsets of patients guided by information gathered this type of real-time immune monitoring. The power of multiplex imaging is the combination of the detailed spatial data it provides and the analytic methods to effectively extract relevant information about single-cell and subcellular level spatial relationships. These entirely new approach was developed by Dr. Komal Das and her student, Vidhya Kewale at the OSUCCC – James.

  • Experts: Komal Das, PhD, research scientist with the Immuno-Oncology Immune Monitorin Discovery Platform, Pelotonia Institute for Immuno-Oncology at the OSUCCC – James)/Vidhya Kewale (undergraduate student)
  • Details: Poster Session 33, Monday, April 17, from 9 a.m. to 12:30 p.m.

BREAST CANCER – RARE FORMS
A-186: Using artificial intelligence to predict response to neoadjuvant chemotherapy in HER2+ breast cancer
Whole-slide imaging and advances in computing technology have enabled the use of artificial intelligence (AI) in pathology – ushering in an era of so-called digital pathology that moves from one-dimensional imaging into three-dimensional imaging of cancer cells with the ability to pair these images with other clinically relevant information. AI can identify and categorize biomarkers, which aids in diagnosis and detection of lymph node metastasis. Predicting therapy response in cancer patients from pre-treatment microscopic examination of the tissue remains a challenging task, limited by poor understanding of the tumor microenvironment. This abstract describes work to develop AI models to predict the effectiveness of neoadjuvant chemotherapy in HER2+ breast cancers. The model first created cells that included 36 markers in the tumor immune microenvironment important for evaluating and targeted treatment options. The team then created an AI pipeline to train machine-learning models to predict chemotherapy response. The system was tested externally for validation with a set of 20 HER2+ breast cancers. They then compared the outcomes against a manual model of evaluation, where pathologists identify and report features. The team’s data showed that the machine-learning model using AI-extracted features outperformed the model using features manually generated by pathologists.

  • Expert: Zaibo Li, MD, PhD, pathologist with the OSUCCC – James and Wexner Medical Center / Anil Parwani, MD, PhD, director of digital pathology at the OSUCCC – James and Wexner Medical Center
  • Details: Poster Session 33, Tuesday, April 18, 1:30-5 p.m.

A-4527 and A-4503: New targets for triple-negative breast cancer (TNBC) treatment
TNBC has limited treatment options that produce durable responses, so the diagnosis is associated with poor prognosis compared to other breast cancer subtypes.

These two abstracts describe laboratory investigations of the role of heparan sulfate and how chemotherapy response can be mitigated to improve chemotherapy effectiveness in TNBC. These findings could guide development of new therapies for TNBC based on inhibition of sulfatase 2 inhibition-eliminate, with more effective responses and fewer side effects.

  • Expert: Jasmine Manochehri (post-doctoral researcher)/Mathew Cherian, MBBS, medical oncologist with the OSUCCC - James
  • Details: Poster section 14, Sunday, April 16, 1:30-5 p.m.

GYNECOLOGIC CANCERS
A-2859: Understanding role of oncogenes in obesity-related endometrial cancers
Endometrial cancer is strongly associated with obesity, with 57% of patients being classified as obese. Rates of both obesity and endometrial cancer are rising in the United States. To better understand the molecular pathways of this disease, scientists are evaluating specific oncogenes- proteins believed to be responsible for driving the development of endometrial cancer. This research aims to provide essential information that could lead to the development of novel strategies for preventing and treating this disease. Data reported in this abstract provides pre-clinical evidence for the development of experimental human studies of exosome-targeted therapies to prevent obesity-related endometrial cancer.

  • Expert: Selvendiran, Karuppaiyah, PhD, scientist with the OSUCCC – James Translational Therapeutics Research Program/Takahiko Sakaue (visiting scholar)
  • Details: Poster Session 30, Tuesday, April 18, 9 a.m.-12:30 p.m.

LIVER CANCER
A-6139: Investigating novel therapeutics that target male sex hormone in liver cancer
Hepatocellular carcinoma (HCC) is the leading form of liver cancer and the fourth-leading cause of cancer-related death worldwide. The disease also occurs 2-4 times more in men than women, something that can be attributed to the male sex hormone: androgen. Previous treatments have utilized “anti-androgen” drugs that block overactivation of androgen receptors thought to be linked to HCC. However, these treatments have failed to have any significant clinical benefit. This abstract describes an alternative, novel approach using small-molecule analogs of niclosamide (pronounced nuh·klow·suh·mide), a drug previously approved by the Food and Drug Administration for treatment of other conditions) to disrupt the androgen receptor. The team developed a pharmacophore model, representing the minimal structure necessary for activity. Overall, the OSUCCC – James team’s data showed that this repurposed drug has promise in slowing HCC growth, presenting a new approach to targeted therapy.

  • Expert: Christopher Coss, PhD, a scientist with the OSUCCC – James Translational Therapeautics Research Program; Pui-Kai (Tom) Li, PhD, scientist with the OSUCCC – James Molecular Carcinogenesis and Chemoprevention Research Program and Jeffrey Cheng (undergraduate student)
  • Details: Poster Section 31, Monday, April 17, from 1:30-5 p.m.

To learn more about research at the OSUCCC – James, visit cancer.osu.edu/research. To learn more about the the AACR annual meeting, visit aacr.org.

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