Biology subjects

Olumoyin, K. D.

Publications and source records attributed to Olumoyin, K. D..

3 recordsLinked to original sources

bioRxiv2026

Ploidy shapes gemcitabine response through altered potency and delayed cell death

Aberrant tumor ploidy is a near-universal hallmark of cancer and increasingly recognized as a determinant of therapeutic response, but the mechanisms by which ploidy shapes sensitivity to specific cytotoxic agents remain unclear. Here, we investigated the relationship between ploidy and therapeutic response using pharmacogenomic reanalysis, isogenic cancer cell systems, live-cell imaging, intracellular pharmacokinetic/ pharmacodynamic (PK/PD) measurements, and mathematical modeling. Across public pharmacogenomic datasets, gemcitabine emerged as a low-ploidy-selective cytotoxic agent. In matched isogenic low- and high-ploidy cell systems, higher-ploidy cells were consistently less sensitive to gemcitabine across multiple lineages. Live-cell imaging and PK/PD measurements in near-diploid and near-tetraploid SUM-159 cells showed that both states formed intracellular dFdCTP, active form of gemcitabine; but, high-ploidy cells exhibited weaker and slower treatment responses, with delayed accumulation of cell death. To quantify these differences, we developed a delay-aware live/dead model driven by intracellular dFdCTP exposure. The model identified both reduced effective gemcitabine potency and a substantially longer delay from intracellular drug action to observed death in high-ploidy cells (17.5 hours in near-diploid cells versus 42.5 hours in near-tetraploid cells). Interpreting these fitted quantities alongside checkpoint signaling and metabolomic profiling suggests that high-ploidy cells convert intracellular gemcitabine exposure less efficiently into replication-stress signaling, nucleotide-metabolic disruption, and cytotoxic commitment. Together, these results establish ploidy as a determinant of both the magnitude and timing of gemcitabine response and provide a quantitative framework for linking intracellular drug exposure to delayed cytotoxic outcomes across ploidy states.

cancer biology↗

bioRxiv2025

A Machine Learning Model Optimized for Local Data Stratifies Patients for the Adoptive Cell Therapy with Tumor Infiltrating Lymphocytes in Bladder Tumors

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a form of personalized immunotherapy that requires ex vivo expansion of autologous TILs and their reinfusion back into the patient. Predicting TIL expansion at the time of diagnosis may improve selection of patients that can benefit from ACT-TIL. It can also prevent high treatment-related costs and delays in treatment of patients whose cancer specimens would not yield successful TIL growth. We developed PETIL, a machine-learning model optimized for data of a medium size to determine a minimal combination of features (demographic, clinical, and biological specimen-based) that is predictive of expansion of TILs from a resected bladder cancer. We used a retrospectively identified set of data from bladder cancer patients at Moffitt Cancer Center for the training and testing cohorts. Additionally, we used data from a recent feasibility clinical trial at Moffitt Cancer Center as a blinded validation cohort. PETIL uses random forest method to identify a combination of robust predictive features, support vector machine model to determine the optimal classification hyperparameters, and Matthews correlation coefficient method to adjust the decision-boundary threshold for imbalanced data. Our model yielded AUC=0.740 for the testing cohort and AUC=0.857 for blinded validation cohort. Thus, our PETIL model optimized for data of medium size has favorable performance metrics for predicting TIL expansion from a given tumor. Authors SummaryTreatment with autologous tumor-infiltrating lymphocytes (TIL) that are expanded ex vivo from a given tumor and then reinfused into the patient is a promising personalized immunotherapy. However, the TIL expansion takes about 4-6 weeks, thus developing tools that predict whether TIL growth will be successful can help to avoid delays in treatment of patients whose cancer specimens would not yield successful TIL expansion. Our Predictor of Expansion of TIL (PETIL) is a machine-learning model that uses patients demographic information, clinical tumor classification, and biological tumor specimen-based measurements to determine a minimal set of these data features that are predictive of TIL expansion outcome. We applied this model to data from bladder cancer patients collected at Moffitt Cancer Center and showed that PETIL has favorable performance metrics for the dataset of a moderate size. This computational predictor can support clinicians in determining which patients are candidates for TIL immunotherapy. The developed PETIL pipeline can also be adjusted to data from other solid tumors.

immunology↗

bioRxiv2024

Visualizing the Spatio-Temporal Dynamics of Clonal Evolution with LinG3D software

Cancer clonal evolution, especially following anti-cancer treatments, depends on the locations of the mutated cells within the tumor tissue. Cells near the vessels, exposed to higher concentrations of drugs, will undergo a different evolutionary path than cells residing far from the vasculature in the areas of lower drug levels. However, classical representations of cell lineage trees do not account for this spatial component of emerging cancer clones. Here, we propose the LinG3D (Lineage Graphs in 3D) algorithms to trace clonal evolution in space and time. These are an open-source collection of routines (in MATLAB, Python, and R) that enables spatio-temporal visualization of clonal evolution in a two-dimensional tumor slice from computer simulations of the tumor evolution models. These routines draw traces of tumor clones in both time and space, with an option to include a projection of a selected microenvironmental factor, such as the drug or oxygen distribution within the tumor. The utility of LinG3D has been demonstrated through examples of simulated tumors with different number of clones and, additionally, in experimental colony growth assay. This routine package extends the classical lineage trees, that show cellular clone relationships in time, by adding the space component to show the locations of cellular clones within the 2D tumor tissue patch from computer simulations of tumor evolution models.

systems biology↗