Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.

Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects. Some anti-angiogenic agents, poly(ADP-ribose) polymerase, and immune checkpoint inhibitors have shown efficacy in early stages of development for the treatment of epithelial ovarian cancer. As demonstrated in recent clinical trials, the use of bevacizumab, cediranib, pazopanib, olaparib, and rucaparib, either alone or in combination with conventional cytotoxic agents, improves progression-free survival. Trials on immune checkpoint inhibitors such as nivolumab have revealed prolonged responses in a small set of ovarian cancer cases but require further exploration. In this review, we discuss the role of targeted therapies against ovarian cancer, including the use of immune checkpoint inhibitors.

N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression.

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45−, and 4′,6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels.

The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.