Takuma Hayashi

Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer

Helicobacter pylori, a gram-negative, flagellated, helical bacterium, is a common cause of chronic gastric infection worldwide. According to the World Health Organization, H. pylori infection, a specific carcinogenic factor, was the leading cause of gastric cancer (GC) in 2014 worldwide (80%). H. pylori infection causes GC in >98% of patients in East Asian countries, including Japan. However, only some types of GCs are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes cytotoxin-associated gene A antigen, which inhibits the nuclear translocation of the breast cancer susceptibility gene 1 and 2 (BRCA1/2), a factor involved in DNA damage repair. This indicated an association between hereditary breast and ovarian cancers (HBOCs) and the development of GC. However, the detailed mechanisms underlying the development of GC caused by H. pylori infection remain unclear. Using the information on hereditary cancers obtained based on cancer genomic medicine, this study revealed that the incidence of GC was high in families with HBOC, with a preponderance for men from families with HBOC. Furthermore, the use of poly-adenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations.

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells

Diagnosis by biopsy is difficult in the ovary since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, the early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the momentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favorable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

Correlation of anti-tumour drug resistance with epigenetic regulation

SummaryDuring treatment, the development of drug-resistant tumours remains an important challenge in cancer treatment. Epigenetic changes have been reported as one of the mechanisms for anti-tumour drug resistance. In clinical practice, a combination of epigenetic-related drugs can be considered as a future selection of cancer therapeutic drugs.