Ingredient Analysis of FDA-Approved Drug Combinations for Pancreatic Adenocarcinoma Using CytoSolve® Systems Architecture

Partner Description

U.S. Food and Drug Administration
The U.S. Food and Drug Administration (FDA) is the regulatory authority responsible for evaluating the safety, efficacy, and scientific rationale of therapeutics advancing toward clinical use. In this case study, FDA involvement reflects downstream regulatory progression of a CytoSolve®-enabled combination therapy for pancreatic adenocarcinoma.

Challenge

Pancreatic adenocarcinoma is a highly aggressive cancer with limited effective treatment options. Gemcitabine, an FDA-approved chemotherapeutic agent, remains a standard of care but exhibits modest efficacy at tolerable doses and significant toxicity at higher concentrations.

The core challenge was ingredient analysis: determining how individual FDA-approved drug ingredients—and their combinations—affect cancer-driving biological processes such as cell proliferation and apoptosis. Traditional discovery methods rely on lengthy, empirical testing of drug combinations, often without mechanistic clarity, making it difficult to identify synergistic ingredient interactions while minimizing toxicity. A scalable, mechanism-driven approach was required to analyze drug ingredients systematically and efficiently.

How CytoSolve® Helped

CytoSolve® applied its systems architecture platform to perform ingredient-focused computational analysis of FDA-approved chemotherapeutic agents relevant to pancreatic cancer biology.

Rather than treating drugs as black-box therapies, CytoSolve® modeled each drug ingredient as a mechanistic perturbation acting on specific molecular targets within independently validated pathway models. Mathematical representations of epidermal growth factor receptor (EGFR) signaling, cell cycle regulation, and apoptosis were computationally integrated, enabling ingredient-level interrogation across cancer-relevant biological processes.

Within this framework, CytoSolve® evaluated how individual drug ingredients influenced tumor cell proliferation and apoptotic signaling, then systematically analyzed ingredient–ingredient interactions across dose ranges. This approach enabled identification of synergistic effects where combined ingredients produced greater apoptotic responses at lower doses than either ingredient alone. The analysis resulted in the formulation of Cyto-001, an in silico–optimized combination of two FDA-approved drug ingredients designed to maximize efficacy while reducing toxicity.

Key Benefits Realized

  • Ingredient-level mechanistic analysis of FDA-approved drugs in pancreatic cancer pathways
  • Identification of synergistic drug ingredient interactions beyond single-agent effects
  • Quantitative evaluation of low-dose ingredient combinations to reduce toxicity burden
  • Rapid narrowing of viable drug ingredients using systems-level evidence
  • Ingredient-focused rationale aligned with regulatory expectations for combination therapies

Outcome

CytoSolve®’s systems architecture delivered a rigorous ingredient analysis that led to the discovery of Cyto-001, a novel combination therapy composed of FDA-approved drug ingredients for pancreatic adenocarcinoma. By embedding individual drugs within a mechanistic, pathway-based framework, the collaboration enabled transparent identification of synergistic ingredient interactions and supported FDA approval for advancement into further clinical trials. This case study demonstrates how ingredient-level systems analysis can transform oncology drug development—accelerating discovery timelines while providing a mechanistically defensible path from computation to regulatory progression.