Comparative genomic analysis of esophageal squamous cell carcinoma and adenocarcinoma: New opportunities towards molecularly targeted therapy

Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two major subtypes of esophageal cancer. ESCC predominantly affects African and Asian populations, which is closely related to chronic smoking and alcohol consumption. EAC typically arises in Barrett's esophagus with a predilection for Western countries. While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer, molecularly targeted therapy is still at the early stages. With the development of large-scale next-generation sequencing, various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied. Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer. In this review, we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer. Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed.

Progress in molecularly targeted anti-tumor drugs derived from natural products or their derivatives / 药学学报

Conventional chemotherapy drugs, molecularly targeted drugs, and immune checkpoint inhibitors are the major constituents of anti-tumor drugs in clinical settings at present. Molecularly targeted drugs specifically target the key proteins, genes, or signal transduction pathways in tumor cells which are essential for initiation and development of tumor, resulting in selective activity to induce cell death or growth inhibition. Molecularly targeted drugs have emerged as the mainstream in the research and development of anti-tumor drugs due to its high selectivity and low toxicity. Natural products refer to the chemical constituents or metabolites originated animals, plants, or microorganisms, which have been recognized as one of the important sources of drug discovery with abundant resources and diversified structures. At present, a number of molecularly targeted anti-tumor drugs derived from natural products or their derivatives have been approved for cancer therapy or in clinical trials. This review will summarize the molecularly targeted anti-tumor drugs derived from natural products or their derivatives according to their different cellular targets, and also outline the molecular mechanism, progress, and perspectives of these drugs.

A Case of Successful Treatment with Kampo Medicine to the Adverse Skin Reactions Induced by Cetuximab / 日本東洋医学雑誌

Molecularly-targeted agents such as cetuximab, an anti-EGFR (epidermal growth factor receptor) monoclonal antibody have been used for the treatment of head and neck cancer. However, these agents frequently induce adverse skin reactions including acne-like rash and paronychia. For these problems, minocycline oral and heparinoid or steroid ointments, are commonly used. Some patients, however, cannot be controlled just by using these drugs. This case report shows a man in his 50s, who was treated for recurrence of nasal cancer. He received a long-term cetuximab therapy for 1 year and a half, and had severe paronychia and skin rash. Medication of unseiin and shiunko ointment decreased these adverse skin reactions, especially, paronychia on his first toes didn't need to be treated by steroid ointment anymore. When the common skin therapies are not effective, these Kampo therapies are possibly one of the options for the supportive care for the patients using cetuximab.

Using Periostin as a Biomarker in the Treatment of Asthma

Periostin acts both as an extracellular matrix protein belonging to the fasciclin family and as a matricellular protein functioning in cell activation by binding to its receptors on the cell surface. It has been established that periostin is a downstream molecule of interleukin (IL)-13, a signature type 2 cytokine, and that periostin plays an important role in the pathogenesis of allergic diseases, including asthma. Based on these findings, much attention has been paid to periostin as a biomarker useful in the treatment of asthma. Periostin is a surrogate biomarker for type 2 immunity; it has been shown that serum periostin can predict the efficacy of anti-IL-13 antibodies (lebrikizumab) and anti-IgE antibodies (omalizumab), and that this usefulness can be potentially expanded to other type 2 antagonists. Moreover, it has been shown that periostin is not a simple surrogate biomarker for type 2 immunity; periostin-high asthma patients have several unique characteristics, including eosinophilia, high fraction of nitric oxide, aspirin intolerance, nasal disorders, and late onset. These characteristics are likely to be correlated with the involvement of periostin in the tissue remodeling of asthma. Periostin is also associated with hyporesponsiveness to inhaled corticosteroids, probably reflecting tissue remodeling. Thus, periostin has 2 characteristics as a biomarker for early diagnosis of asthma: surrogate biomarkers for type 2 immunity and tissue remodeling. Based on these characteristics, we will be able to apply serum periostin to treatment of asthma.

Curative Resection Following Neoadjuvant Chemotherapy Including a Molecularly Targeted Agent in Patients with Unresectable Colorectal Distant Metastases

PURPOSE: A colorectal carcinoma is the fourth most common malignancy in the world. Unfortunately, only approximately 20% of the liver metastases are resectable at the initial presentation. Neoadjuvant chemotherapy has been used for downsizing in unresectable disease. In addition, the use of newer biologic agents, such as cetuximab and bevacizumab, has much improved responses in patients with unresectable colorectal liver metastases. The aim of this study was to report on patients who had received a curative resection following neoadjuvant chemotherapy including a molecularly targeted agent for unresectable colorectal liver metastases. METHODS: Following the neoadjuvant chemotherapy using cetuximab plus FOLFIRI (irinotecan and infused fluorouracil plus leucovorin) or bevacizumab plus FOLFOX (oxaliplatin and infused fluorouracil plus leucovorin), 10 patients with initially unresectable colorectal liver metastases underwent a curative surgical resection between September 2005 and June 2007. RESULTS: One patient underwent a right lobectomy, three patients a segmentectomy and five a wedge resection with or without radiofrequency ablation. With a median postoperative follow-up of 14 months (range, 1 to 22 months), five recurrences (50%) occurred. The common toxic effects were grade 2/3 skin toxicity (60%), grade 4 hematologic toxicity (20%), grade 3 gastrointestinal toxicity (10%), and grade 3 neurologic toxicity (10%). CONCLUSIONS: Our preliminary data suggests that neoadjuvant chemotherapy including a molecularly targeted agent may improve resectability in patients with initially unresectable colorectal liver metastases although a high recurrence rate exists. Randomized prospective studies comparing neoadjuvant chemotherapy including a targeted agent in cases of unresectable colorectal liver metastases are warranted.