Understanding mechanisms driving the stressor-to-phenotype phenomena and controlling these maladaptive responses in the wake of stressor presentation may lead to the development of rational therapeutic approaches to abrogate dysfunction from interactomes to connectomes.

The combination of drug (e.g., PU-H71), companion diagnostic (e.g., [¹²⁴I]-PU-H71 for solid tumors (Pillarsetty et al. 2019; Jhaveri et al. 2020) and PU-FITC for hematologic malignancies (Merugu et al. 2020; Sugita et al. 2021) and biomarker (e.g., epichaperome levels (Rodina et al. 2016)) enables a precision medicine approach in epichaperome therapy that is based of stressor-induced molecular dysfunctions rather than genetics or pathology. Taking lessons from oncology paradigms, a similar platform was also designed for neurodegenerative disorders (Inda et al. 2020; Bolaender et al. 2021).

On the cover: Essential to normal cellular function is the interaction among proteins and their organization in well-defined networks. Pillarsetty et al. (pp. 559–573) introduced a positron emission tomography-based assay called PU-PET to visualize pathologic protein-protein interaction networks termed epichaperomes in human cancer patients. They demonstrate epichaperome engagement by the drug candidate PU-H71 in patients’ tumors at single-lesion resolution and show how information derived from PU-PET provides a platform for precision medicine targeting of the aberrant properties of protein networks. Artwork by Samantha Welker and Samantha Gore. [courtesy of Cancer Cell]