Research Advances from the Physical Sciences – Oncology Network (PS-ON)

Using mathematical modeling, researchers with the Moffitt PS-ON Center found that tissue architecture determines cancer evolution. The findings reveal that tumor location plays an important role in the development and progression of cancer.  

Butner et al. with the Houston Methodist PS-ON Project developed a mathematical model that predicts responses immunotherapy in individual patients. This tool could potentially help oncologists in designing treatment plans. 

By integrating computational modeling and experimental approaches, researchers with the Dana-Farber PS-ON Center identified the optimal dosing schedule for a cancer combination therapy of osimertinib (an EGFR inhibitor) and dacomitinib (a HER inhibitor) to treat patients with non-small cell lung cancer. This dosing schedule is currently being tested in a Phase I clinical trial. 

Researchers with the MD Anderson Cancer Center PS-ON Project developed a mathematical framework to connect what happens to tumors after treatment with the recurrence patterns observed in clinical trials. According to the authors of the study, this work could "provide insights as to why particular clinical trials failed and guide how to redesign them for success."

Alfonso et al. with the Moffitt PS-ON Project developed and validated a computational model of tumor-immune ecosystem dynamics that predicts cancer responses to radiotherapy.

Using longitudinal single-cell RNA sequencing and state-transition theory, Frankhouser et al. with the City of Hope PS-ON Project showed that clinically relevant chronic myeloid leukemia (CML) phenotypes emerge when cellular data are aggregated into macro-states, even though individual cells occupy continuous transcriptional micro-states. According to the authors of the study, "this framework provides insights into CML progression and offers a broadly applicable strategy for exploring disease dynamics across cancers and other complex conditions."

Tabdanov et al. with the University of Minnesota PS-ON Center engineered T cells to enhance their 3D migration through complex tumor microenvironments, which may be used to enhance the efficacy of immunotherapies. 

Shah et al. with the Cornell and Dana-Farber PS-ON Centers revealed a mechanism linking confined cell migration during metastasis with DNA damage. 

Using an experimental model that mimics human blood vessels, investigators with the MIT PS-ON Project showed how the cancer cell glycocalyx (i.e., sugar coating) promotes steps in metastasis, specifically adhesion to and extravasation from blood vessels.  

Investigators supported through the UCSF PS-ON Project developed MechanoAge and Mechano-RISQ, which combine single-cell mechanical measurements with machine learning to identify individuals who may have a higher risk of developing breast cancer. This approach could complement existing breast cancer risk tools by measuring physical changes in aging breast cells. 

Phan et al. with the University of Pennsylvania PS-ON Project found that cell confinement initiates a delayed but heritable loss of chromosomes. The findings suggest that the crowded, compressed environment inside solid tumors may contribute to genetic changes that allow cancers to evolve over time.

Investigators with the Memorial Sloan Kettering Cancer Center PS-ON Project contributed to a collaborative effort that developed an early cancer detection assay for LINE-1 ORF1p, a transposon protein that is a biomarker of multiple cancers.  

Researchers with the University of Pennsylvania PS-ON Project revealed a mechanism by which stiff matrix induces exosome secretion to promote tumor growth. 

Using computational and experimental approaches, researchers with the Columbia PS-ON Center found that a subtype of glioblastoma tumors are powered by overactive mitochondria and vulnerable to drugs currently being tested in cancer clinical trials. 

Rajurkar et al. with the MSKCC PS-ON Project found that 3TC (a reverse transcriptase inhibitor and HIV drug) disrupts the oncogenic functions of repeat RNAs and tumor progression in metastatic colorectal cancer.

Using a 3D human ovarian cancer model, researchers with the Northeastern University PS-ON Project found that cancer-targeted photoimmunotherapy reduces tumor spheroid size while preserving significantly more immune cells.

Researchers with the Houston Methodist Research Institute PS-ON Project developed the High-throughput Single-Cell Omni-functional Profiling Engine (HiSCOPE), a modular microfluidic platform that measures the functional dynamics of more than 10,000 individual cells and permits selected live cells to be retrieved for additional analysis. Using HiSCOPE, they examined leukemia cell drug responses natural killer cell functions, and interactions between T cells and macrophages.