Most patients with non‐small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR‐TKI), and their sensitivities to various EGFR‐TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR‐TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3‐L858R), L861Q (Ba/F3‐L861Q) or S768I (Ba/F3‐S768I) mutations were created and their drug sensitivities to various EGFR‐TKI were examined. Both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line. The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations.

We have found that intestinal bacteria and their metabolites, short‐chain fatty acids (SCFAs), promote cancer growth in prostate cancer (PCa) mouse models. To clarify the association between gut microbiota and PCa in humans, we analyzed the gut microbiota profiles of men with suspected PCa. One hundred and fifty‐two Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: a discovery cohort (114 samples) and a test cohort (38 samples). The gut microbiota was compared between two groups, a high‐risk group (men with Grade group 2 or higher PCa) and a negative + low‐risk group (men with negative biopsy or Grade group 1 PCa), using 16S rRNA gene sequencing. The relative abundances of Rikenellaceae, Alistipes, and Lachnospira, all SCFA‐producing bacteria, were significantly increased in high‐risk group. In receiver operating characteristic curve analysis, the index calculated from the abundance of 18 bacterial genera which were selected by least absolute shrinkage and selection operator regression detected high‐risk PCa in the discovery cohort with higher accuracy than the prostate specific antigen test (area under the curve [AUC] = 0.85 vs 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs 0.67). The specific bacterial taxa were associated with high‐risk PCa. The gut microbiota profile could be a novel useful marker for the detection of high‐risk PCa and could contribute to the carcinogenesis of PCa.

Non-small cell lung cancer (NSCLC) carrying echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangements is hypersensitive to ALK inhibitors, including crizotinib and alectinib. Crizotinib was initially designed as a MET inhibitor, whereas alectinib is a selective ALK inhibitor. The MET signal, which is inhibited by crizotinib but not by alectinib, is dysregulated in many human cancers. However, the role of the MET signal in ALK-positive NSCLC remains unclear. In this study, we found that hepatocyte growth factor (HGF), ligand of MET, mediated the resistance to alectinib, but not to crizotinib, via the MET signal in ALK-positive NSCLC cell lines (H3122 and H2228 cell lines). In addition, alectinib activated the MET signal even in the absence of HGF and the inhibition of the MET signal enhanced the efficacy of alectinib. These findings suggest that activated MET acts as a salvage signal in ALK-positive NSCLC. This novel role of the MET signal in ALK-positive NSCLC may pave the way for further clinical trials examining MET inhibitors.

The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country. Lifestyle, especially diet, plays an important role in the development and progression of prostate cancer. Recent studies have revealed a connection between the gut microbiome and prostate cancer. A high-fat diet causes gut dysbiosis and gut bacterial metabolites, such as short-chain fatty acids and phospholipids that enter systemic circulation result in promoting prostate cancer growth. Additionally, the gut microbiota can serve as a source of testosterone, which affects prostate cancer progression. Men with castration-resistant prostate cancer have an increased abundance of gut bacteria with androgenic functions. Men with high-risk prostate cancer share a specific gut microbial profile and profiling gut microbiota could be a potentially effective tool to screen men with high-risk prostate cancer. Lifestyle modifications can improve the gut microbiome. Furthermore, altering the gut microbiome using prebiotic or probiotic interventions may prevent or delay prostate cancer development. Further study into the "Gut-Prostate Axis" would help in the discovery of new strategies for the prevention, screening, and treatment of prostate cancer.

Enfortumab vedotin is a novel antibody–drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p = 0.031) and cancer-specific mortality (p = 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20–7.98; p = 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression.