Targeting hypoxic habitats with hypoxia pro drug evofosfamide in preclinical models of sarcoma

Tumor habitats are phenotypically and spatially distinct intratumoral regions. Hypoxic habitats are associated with reduced accessibility of chemotherapeutics, resulting in resistance. Hypoxia targeted prodrugs (HAPs) may overcome this resistance. However, in a phase III clinical trial, the HAP evofosfamide (TH-302) did not improve survival of sarcomas when used in combination with the standard of care doxorubicin (Dox). This may have been due to a lack of patient stratification based on hypoxic status. Thus, identification of hypoxic tumor habitats (Jardim-Perassi et al. 2019) would allow for pre-therapy patient stratification, and monitoring of habitats post-therapy. Our goal was to use multiparametric (mp) MRI and co-registered histology to classify hypoxic habitats in preclinical models of sarcoma, and to use Habitat Imaging to monitor therapy response. A patient-derived xenograft (PDX) of rhabdomyosarcoma …