ZRANB1 is an NBS1 deubiquitinase and a potential target to overcome radioresistance and PARP inhibitor resistance in triple-negative breast cancer

Poly(ADP-ribose)polymerase inhibitors(PARPi)are used to treat ovarian cancer and triple-negative breast cancer(TNBC)with defective homologous recombination repair pathways.However,de novo and acquired PARPi resistance limits clinical benefits.1 The MRE11-RAD50-NBS1(MRN)complex mediates the sensing,processing,and signaling of DNA double-strand breaks(DSBs)and plays important roles in the efficacy of PARPi and radiation treatment,2 and yet the mechanisms for the regulation and degradation of the MRN complex are not well understood.ZRANB1,also known as Trabid,is a breast cancer-promoting deubiquitinase that preferentially cleaves K29-,K33-,and K63-linked ubiquitin chains,3 but its role in therapy resistance remains unknown.

Symptoms predicting health-related quality of life in prostate cancer patients treated with localized radiation therapy

Objective:Patient-reported health-related quality-of-life(HRQOL)measures can provide guidance for treatment decision making,symptom management,and discharge planning.HRQOL is often influenced by the distress experienced by patients from disease or treatment-related symp-toms.This study aimed to identify symptoms that can predict changes in HRQOL in men undergo-ing external beam radiation therapy(EBRT)for nonmetastatic prostate cancer(NMPC).Methods:Fifty-one men with NMPC scheduled for EBRT were assessed at the baseline,at the midpoint of EBRT,and at the end of EBRT.All participants received 38-42 daily doses of EBRT(five times a week),depending on the stage of their disease.Validated questionnaires were administered to evaluate depressive symptoms,urinary and sexual functions,bowel issues,symp-tom-related distress,fatigue,and HRQOL.Pearson correlations,repeated-measures ANOVA,and multiple regressions examined the relationships among variables.Results:Intensification of symptoms and increased symptom-related distress,with a corre-sponding decline in HRQOL,were observed during EBRT in men with NMPC.Changes in symp-toms and symptom distress were associated with changes in HRQOL at the midpoint of EBRT(r=-0.37 to-0.6,P=0.05)and at the end of EBRT(r=-0.3 to-0.47,P=0.01)compared with the baseline.The regression model comprising age,body mass index,Gleason score,T category,androgen-deprivation therapy use,radiation dose received,symptoms(urinary/sexual/bowel prob-lems,fatigue),and overall symptom distress explained 70%of the variance in predicting HRQOL.Urinary problems and fatigue significantly predicted the decline in HRQOL during EBRT.Conclusion:Identifying specific symptoms that can influence HRQOL during EBRT for NMPC can provide feasible interventional targets to improve treatment outcomes.