New Role of Therapy for Deceleration of Tumor Phenotype Progression
Presentations
PO-GePV-T-445 (Sunday, 7/10/2022) [Eastern Time (GMT-4)]
ePoster Forums
Purpose: According to NIH SEER data, current therapeutic schemas for distant advanced cancer induce acutely potent yet only short-lived responses and cannot prevent tumor recurrence. Therapy induces the transformation of any residual tumor cells to more aggressive and resistant phenotypes, and helps tumor cells colonize to distant sites via hematogenous circulation and systemic immunosuppressive effects. In this new light of therapy’s dual positive and negative roles, we propose a new therapy design not to achieve tumor extinction, but to slow down tumor progression.
Methods: We consider two different mathematical models of tumor phenotype progression. In a linear model tumor phenotype evolution is depicted by a linear chain and in a network model the tumor phenotypes and their transition are mapped to nodes and edges on a network. In mathematical models, the evolution of tumor phenotypes is primarily driven by the dual role of therapy, elimination of tumor cells and acceleration of tumor phenotype progression. We consider tumor extinction as a rare event and use a large deviation theory to calculate the mean passage time to the most aggressive tumor phenotype.
Results: We shows the existence of the intermediate range of therapeutic dosing schema where tumor elimination and tumor progression can be delicately balanced. In the low dose regime, tumor phenotype does not progress, but tumor population size grows indefinitely. In the high dose regime, tumor phenotype composition undergoes a dramatic change from the sensitive and benign phenotype to the resistant and more malignant phenotype. Finally, we propose the changed new shape of tumor control probability as a function of dose, from a sigmoidal curve to a Gaussian curve centered around optimal dosing.
Conclusion: The current treatment schema focuses on tumor elimination, but potentially induce the tumor phenotypic progression. We show therapy can be re-designed to slow down tumor progression.
Keywords
Not Applicable / None Entered.
Taxonomy
TH- Radiobiology(RBio)/Biology(Bio): RBio- LQ/TCP/NTCP/outcome modeling
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