Since the approval and introduction of imatinib as the first molecular-targeted drug for the treatment of chronic myelogenous leukemia in 2001, more than 50 cancer targeted drugs have been approved in Japan. The molecular targeted drugs have shown prominent efficacy in several cancers caused by the corresponding target molecules. Over recent years, development of biomarkers, companion diagnostics, and next generation sequencing analysis for prediction of clinical outcome facilitated the selection of appropriate drug for patients. The molecular targeted drugs are classified into two groups, monoclonal antibodies and small molecules, which have various mechanisms of action, including inhibition of tyrosine kinases, tumor angiogenesis, and immune checkpoint. Various mechanisms of action of drugs may also exhibit unique adverse events that have not been previously observed. Continuous changes in cancer genomes lead to tumor heterogeneity, which in turn may fuel drug resistance. To overcome these issues, identification of new therapeutic targets and a large number of clinical trials with novel designs are in progress for realization of cancer precision medicine. Here, we summarize recent findings of molecular targeted drugs.

Recent studies have elucidated the pathophysiology of the common placental disorders. It is believed that gestational hypertension, also known as preeclampsia, is a two-stage disease. Inadequate migration of the trophoblasts induces defective remodeling of the uterine spiral arteries. The poorly perfused and re-perfused placenta (Stage 1) produces antiangiogenic factors that cause maternal endothelial dysfunction (Stage 2). It has been hypothesized that a luck of fetomaternal immune tolerance leads to insufficient trophoblastic differentiation.

Another placental disorder is chronic villitis or villitis of unknown etiology. The diagnosis of severe chronic villitis is important to the clinician because it causes intrauterine growth restriction, fetal death, and neonatal neurological impairment. These lesions could be of immune origin. It has been reported that the pathogenesis of chronic placentitis is the maternal anti-fetal cellular and antibody-mediated rejection.

Disorders of gestational immune tolerance underlie these two placental diorders.

As of February 2018, 333 pancreatic transplantations from brain-dead donors have been performed in Japan. Of these, 63 were performed at our institution between January 2001 and February 2018. Simultaneous pancreas and kidney transplantation (SPK) was performed in 54 patients and pancreas after kidney transplantation (PAK) was performed in 9 patients. The operative time was significantly longer for SPK than for PAK (SPK 390 min, PAK 266 min: p = 0.00016). Transplanted pancreas graft loss occurred in 9 of 54 SPK cases (16.7%), and in 5 of 9 PAK cases (55.6%). The causes of graft loss were thrombosis, rejection, infection, recurrence of type1 diabetes, and pancreatitis. The 1-, 3-, 5-, and 10-year pancreatic graft survival rates for SPK were 92.3%, 87.7%, 83.1%, and 71.1%, respectively, and the 1-, 3-, and 5-year pancreatic graft survival rates for PAK were 55.5%, 55.5%, and 37.0%, respectively. Both of pancreatic and renal graft survival rates in our institution were higher than those of US/non-US and Japan. The patient survival rate was also higher in our institution. As pancreatic transplantation is currently considered the optimal treatment for type 1 diabetic patients, improvement of graft survival is an urgent issue.