Screening and Validation of Molecular Targeted Radiosensitizers

Abstract

The development of molecular targeted drugs with radiation and chemotherapy is critically important for improving the outcomes of patients with hard-to-treat, potentially curable cancers. However, too many preclinical studies have not

Pencil beam scanning proton FLASH maintains tumor control while normal tissue damage is reduced in a mouse model

“…From a biological point of view, TGD and tumor control are two very different endpoints [28]. In a TGD assay, the radiation effects on the bulk tumor cells are assessed, but not the inactivation of the clonogenic tumor cells, cancer stem cells (CSC) [28,29]. In contrast, permanent tumor control after RT depends, amongst others, on the inactivation of all CSC in the tumor, and therefore tumor control assays functionally assess the effect of radiation on the inactivation of CSC [30].…”

Targeting PARP for Chemoradiosensitization: Opportunities, Challenges, and the Road Ahead

“…1). Another possibility is that there is inter-tumoral heterogeneity in the radiosensitizing effects of PARP inhibitors and predictive biomarkers will be needed to identify patients most likely to benefit from treatment intensification [5]. These may be biomarkers mechanistically related to the effects of PARP inhibitors, for example proliferation indices or DDR factors indictive of a dependency on PARPmediated DNA repair.…”

“…There exist considerable challenges to clinical translation of combining targeted drugs with CRT or RT that the field has only recently begun to fully appreciate [4,5].…”

Tumor Heterogeneity Research and Innovation in Biologically Based Radiation Therapy From the National Cancer Institute Radiation Research Program Portfolio

“…Several investigators are well along the path of clinical trials on the basis of preliminary data reflecting uniformly mandated National Institute of Standards and Technology traceable dosimetry. [50][51][52][53][54][55] Additionally, NCI via the Small Business Innovation Research program has supported the development of radioprotectors 29 and radiosensitizers. 56…”