Abstract A016: Heterogeneity of drug sensitivity profiles of two primary and metastatic tumors
Authors: Rajeshwar Nitiyanandan, Chiara Maestri, Jahanvi Kumar, Ricardo Parker, Ivan Trus, Dr. William Cance, Dr. Chris Apfel
Journal: Cancer Research (2025)

Abstract Background Tumor heterogeneity is a key driver of drug resistance in late-stage cancers and metastases are often thought to exhibit distinct sensitivity and resistance profiles compared to primary tumors. We developed a live 3D microtumor functional profiling model that preserves the tumor microenvironment and provides clinically relevant results within 7 to 10 days. While this model reflects the heterogeneity of a patient’s biopsy, it remains uncertain whether changes in mutation profiles may translate into meaningful differences in drug sensitivity and resistance. Material &amp; Methods We quantified the in-vitro sensitivity and resistance profiles of a primary tumor and the corresponding peritoneal metastasis of a patient with ovarian cancer and a primary tumor and the corresponding lung metastasis of a patient with colorectal cancer. Viable specimens were cooled and shipped overnight, processed the following day, and exposed to tumor-specific NCCN guideline-recommended therapies at various concentrations. Tumor viability was assessed after 72 hours of exposure. Results For the ovarian cancer samples, drug sensitivity between the primary tumor and peritoneal metastasis showed a high correlation (Spearman’s ρ = 90.0%, p&amp;lt;0.001). Cyclophosphamide (84% in the primary and 71% in the metastasis), doxorubicin (66% and 59%), carboplatin (41% and 28%) and oxaliplatin (58% and 47%) emerged as the most effective agents, while paclitaxel (14% and 2%), docetaxel (6% and 3%), and gemcitabine (5% and 2%) demonstrated clear in-vitro resistance. While there was also a statistically significant correlation between the primary and the metastasis in the colorectal cancer samples (Spearman’s ρ = 31.4%, p=0.002) with cyclophosphamide (94% and 84%) showing high sensitivity and paclitaxel (3% and 1%) tumor resistance in both specimens, there were several drugs e.g. oxaliplatin (18% and 81%) that were more effective in one or the other specimen. Interpretation Our findings suggest that drug sensitivity and resistance profiles between primary tumors and their local metastases (e.g., peritoneal spread) may be highly similar, implying that biopsy location may be less critical in such cases. However, hematogenous metastases to distant organs (e.g., lung) may exhibit substantially different profiles, potentially reflecting biological changes such as epithelial-mesenchymal transition, underscoring the importance of considering both a primary and metastatic site to cover the full sensitivity and resistance profile of such late-stage cancers. Citation Format: Rajeshwar Nitiyanandan, Chiara Maestri, Jahanvi Kumar, Ricardo Parker, Ivan Trus, Dr. William Cance, Dr. Chris Apfel. Heterogeneity of drug sensitivity profiles of two primary and metastatic tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A016.