Highlights of This Issue

Abstract

Factors influencing the efficacy of abiraterone in suppressing tumor growth in castration-resistant prostate cancer (CRPC) are not well understood. Based on its steroidal structure, Mostaghel and colleagues hypothesized that abiraterone may be transported by the SLCO family of androgen transporters. In vitro, prostate cancer cells expressing SLCO2B1 showed higher abiraterone uptake when compared with controls. In a neoadjuvant trial of abiraterone prior to prostatectomy, genetic variation in SLCO2B1 was associated with tissue abiraterone levels and rates of minimal residual disease. These data suggest variation in SLCO genes may serve as predictors of response to abiraterone treatment in men with CRPC.KRAS mutation was reported as a contributor to acquired cetuximab resistance in metastatic colorectal cancer. To explore whether other mutations in genes downstream of EGFR confer acquired resistance to cetuximab-based therapy, Xu and colleagues designed a strategy to identify low-frequency candidate mutations that are associated with acquired cetuximab resistance by sequencing circulating tumor DNA taken from patient plasma samples obtained before and during treatment. Five novel mutations in exon 19 and hotspot PIK3CA mutations were identified, which contribute to acquired cetuximab resistance. The role of PIK3CA mutations in acquired cetuximab resistance appears to be comparable with that of KRAS mutations.In patients treated with pembrolizumab, tumor burden increase of less than 20% from baseline during therapy was noted in 55% of the patients and was associated with longer overall survival, proposing a practical prognostic marker that may objectively guide treatment decisions. Pseudoprogression was noted in 4 among 107 patients (4%), including one patient without measurable tumor burden at baseline, which is indicative of a need for increased attention to nonmeasurable tumor burden in the context of immunotherapy.Reliable and reproducible methods for detecting PD-L1 expression in tumors is crucial for identifying patients who respond to anti-PD-1 therapy. The PD-L1 IHC 22C3 pharmDx is a companion diagnostic developed by Dako to identify non-small cell lung cancer patients who are likely to derive benefit from treatment with pembrolizumab. Using this assay, Cooper and colleagues investigated the inter- and intra-observer reproducibility of pathologists' assessment of PD-L1 staining and the impact of training on reproducibility. They demonstrated good agreement at both 1% and 50% cut-points. A one-hour training session had minimal impact on the reproducibility.