Model-informed experimental design recommendations for distinguishing intrinsic and acquired targeted therapeutic resistance in head and neck cancer.

ABSTRACT: The promise of precision medicine has been limited by the pervasive resistance to many targeted therapies for cancer. Inferring the timing (i.e., pre-existing or acquired) and mechanism (i.e., drug-induced) of such resistance is crucial for designing effective new therapeutics. This paper studies cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) using tumor volume data obtained from patient-derived tumor xenografts. We ask if resistance mechanisms can be determined from this data alone, and if not, what data would be needed to deduce the underlying mode(s) of resistance. To answer these questions, we propose a family of mathematical models, with each member of the family assuming a different timing and mechanism of resistance. We present a method for fitting these model

SUBMITTER: Cardenas SD 

PROVIDER: S-EPMC9458753 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature