Elucidating spatiotemporal dynamics of nascent extracellular matrix in response to platinum treatment in ovarian cancer

Active Project Grant Awarded Last action

Award ID
R37CA291976
Recipient
Awarding agency
Obligated
$1,130,356

Award facts

Assistance listing
93.394 Cancer Detection and Diagnosis Research
Completion date 29% complete
Place of performance
Sioux Falls, SD 57104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
High-grade serous ovarian carcinoma (hgsc) is the most common type of ovarian cancer and has the 3RD highest mortality-to-incidence ratio of all cancers. Even with resection and aggressive platinum-based chemotherapy treatment, tumor recurrence occurs in 70% of patients, as a result of aberrant extracellular matrix (ECM) production leading to chemotherapy resistance. While the unidirectional effects of a dysregulated ECM composition and structure are well documented to contribute to cancer's ability to resist treatment, knowledge on the effect of chemotherapy on spatial and temporal changes of the ECM remains limited. A main reason for this limitation is the lack of technologies that can track spatiotemporal dynamics of newly synthesized ECM in response to treatment in a biologically relevant yet controlled manner. In studies leading to this application, we have optimized platforms combining biomimetic tissue engineered cancer CO-cultures and metabolic labeling allowing to track newly synthesized ECM dynamics in response to treatment and further implicate mechanotransduction signaling with the dysregulated ECM. Our translational approach includes well annotated and characterized hgsc cell lines and patient-derived xenograft (PDX) lines, as well as primary hgsc and PDX tumor biopsies. We will utilize innovative engineering approaches, metabolic labeling of newly synthesized proteins and state-of-the-art super resolution confocal imaging, proteomics from enriched newly synthesized proteins, machine-learning image analysis, flow cytometry, biomechanical characterization, and immunohistochemistry analysis to test our hypothesis. Specific aims are to identify platinum-induced spatiotemporal dynamics of newly synthesized ECM, determine how platinum-induced alterations in cell-ECM mechanotransduction relate to hgsc chemoresistance, and elucidate how ECM dynamics differ between platinum sensitive and platinum resistant hgsc tumors. Through these studies, we expect to have an important positive impact by opening new horizons for development of more efficacious ECM-targeted agents to mitigate hgsc chemoresistance, monitor treatment response, and ultimately improving chemotherapy effectiveness and mitigating chemoresistance.

Transactions

Action Obligated Date
Amendment $546,275
Original award $584,081

Subawards

Subrecipient Amount Awarded
The University Of South Dakota USD will assist in the analysis of imaging and multi-OMICs datasets, including metabolic labeling and any datasets related to the functional characterization of… $55,007
The Regents Of The University Of Colorado Colorado will collaborate with Sanford to evaluate the biomechanical changes of platinum treatment on nascent ECM remodeling, by evaluating scaffolds, matrix… $64,740
Regents Of The University Of Michigan Michigan has significant expertise in identifying molecular mechanisms that control the pathogenesis of ovarian cancer, with the goal of developing novel… $52,285

Quick answers

Who received award R37CA291976?

R37CA291976 was awarded to Sanford Research by National Cancer Institute (National Institutes of Health) on May 12, 2025.

How much is award R37CA291976 worth?

$1,130,356 has been obligated on R37CA291976.

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