Abstract 2557: Age of host and its impact on progression and treatment response in tumors derived from early or late onset Hispanic colorectal cancer patients
Authors: Lesly Torres-Gonzalez, Shivani Soni, Goar Symbatyan, Jae Ho Lo, Pooja Mittal, Unnati Hemant Shah, Francesca Battaglin, Karam Ashouri, Sandra Algaze, Priya Jayachandran, Wu Zhang, David W. Craig, Julie Culver, Mariana C. Stren, John D. Carpten, Bodour Salhia, Heinz-Josef Lenz
Journal: Cancer Research (2025)

Abstract Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and causes of cancer-related death in the Hispanic/Latino (H&amp;L) population. Rates of early onset (&amp;lt;50, EO) CRC have increased more rapidly in H&amp;L than other ethnic and racial groups. EO CRCs are often diagnosed at advanced stages, suggesting a more aggressive tumor biology. Investigations on the effect of age within both the tumor and host environments could provide insight into key differences between EO and late onset (&amp;gt;50, LO) CRCs. Our study (Cancer Moonshot Program), explores how both age of the host and tumor intrinsic factors influence growth, progression, and treatment response. Methods: CRC patient derived xenograft (PDX) models were selected from our biorepository based on race and age. Tumor samples from an EO 36 year old (young patient, YP) and a LO 66 year old (old patient, OP) H&amp;L male were expanded using 2 month old NSG mice. Following expansion, each tumor was then implanted into both young (2 months, YM) and old male NSG mice (13-14 months, OM) to establish four PDX models: YP in YM, OP in YM, YP in OM, and OP in OM. Each model was treated with oxaliplatin (6mg/kg), 5-fluorouracil (5-FU, 50mg/kg), or vehicle (control) twice a week for four weeks and monitored for survival. Tumor volume was measured twice per week until an endpoint of 15mm at any diameter was reached. Tumor tissue and blood samples were collected and used for metabolomic and epigenomic analysis. Results: Initial patient tumor expansion showed differing tumor growth rates between YP and OP tumors, with each being ready for mouse implantation at 63 and 90 days respectively. In all models, control mice had significantly higher tumor growth rates compared to treatment groups (p&amp;lt;0.01), except in the 5-FU treated OP in OM. Survival analysis showed significantly increased survival in treatment groups for YP in YM and YP in OM (p&amp;lt;0.05). Within each treatment group, YP in YM showed significantly increased tumor growth when compared to other models (p&amp;lt;0.01). Additionally, OP in YM also showed significantly reduced growth in the 5-FU treatment group compared to other groups (p&amp;lt;0.05). Conclusion: Our current findings showed that all patient tumor-mouse host age combinations showed significant tumor growth reduction when treated with oxaliplatin or 5-FU, except in 5-FU treated OP in OM. The YP in YM model displays significantly more aggressive tumor growth regardless of the treatment given. However, comparison of treatments to control in YP in YM show significant tumor growth reduction and increased survival, suggesting a more effective response to treatments. The similarity in growth rates of the three other models, regardless of treatment, may suggest that the aggressive characteristics of YP in YM are influenced by both the host and tumor. Further studies are warranted to understand the modifications that influence the observed differences. Citation Format: Lesly Torres-Gonzalez, Shivani Soni, Goar Symbatyan, Jae Ho Lo, Pooja Mittal, Unnati Hemant Shah, Francesca Battaglin, Karam Ashouri, Sandra Algaze, Priya Jayachandran, Wu Zhang, David W. Craig, Julie Culver, Mariana C. Stren, John D. Carpten, Bodour Salhia, Heinz-Josef Lenz. Age of host and its impact on progression and treatment response in tumors derived from early or late onset Hispanic colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2557.