RESUMEN
Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10% of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.
RESUMEN
BACKGROUND: The prognostic value of polybromo 1 (PBRM1) gene mutations in clear cell renal carcinoma (CCRCC) with anti-programmed death-ligand 1 (PD-L1) therapy remains controversial, and few studies have reported the impact of PBRM1 mutations in other cancer types. METHODS: The patient information was obtained from cBioPortal and the Tumor Immune Estimation Resource (TIMER) databases. Mann-Whitney U test were used for correlation analysis. For survival analyses, Kaplan-Meier survival curves were used and compared using the log-rank test. Cox's regression model was used to perform univariable and multivariable analyses. RESULTS: Our study, for the first time, performed comprehensive analyses of PBRM1 mutation frequency, PBRM1 expression, relationship of PBRM1 mutations with clinical benefit from immunotherapy, and PBRM1 expression with immune infiltrates in diverse cancer types. The results showed that the expression of PBRM1 was significantly lower in diverse cancer types compared with normal tissues. Based on multivariable analysis, PBRM1 mutations trended towards worse clinical outcomes from anti-PD-L1 in CCRCC, lung adenocarcinoma (LUAD), bladder urothelial carcinoma (BLCA), and skin cutaneous melanoma (SKCM), and a significant association was observed in LUAD and BLCA. PBRM1 mutations were associated with higher TMB in diverse cancer types and significant associations were observed in LUAD and BLCA. The expression of PBRM1 was found to positively correlate with immune infiltrates in diverse cancer types. CONCLUSIONS: Our findings suggested caution in starting immunotherapy alone in PBRM1 mutant patients. Further studies are needed to improve treatment for PBRM1 mutant patients.