| 内容 |
胃がん全体の約10%を占めるスキルス胃がんは、びまん性に胃壁内を進展するため早期発見が難しく、強い間質増生と線維化を伴い、高頻度に腹膜播種と呼ばれる転移を起こす。5年生存率は約10%程度と低く、日本に多い予後不良の難治がんである。特に、腹膜播種を起こした患者の平均生存期間は数ヶ月程度であり、がん性腹水貯留や腸閉塞などを合併するためQOLが著しく低下する。スキルス胃がんの進展や腹膜播種の分子機構は十分に分かっておらず、有効な治療法が確立されていない。従って、スキルス胃がんの生物学的特性を標的とした、新しいコンセプトによる治療法開発が求められている。
我々は、リン酸化プロテオミクス解析やがん間質相互作用の解析から、スキルス胃がんの浸潤や腹膜播種の分子機構の解明と制御法の開発に取り組んできた。実際に、スキルス胃がんの腹膜播種に関わる分子を複数同定し、治療薬の候補となる抗体や化合物を得ることに成功した。また最近は、マルチカラー蛍光細胞系譜解析により、スキルス胃がん腹膜播種腫瘍のクローン性や転移機序の解析を試みており、興味深い知見が得られている。本セミナーでは、これらの研究成果について紹介したい。
Scirrhous gastric carcinoma (SGC), accounting for approximately 10% of all gastric cancers, is difficult to detect early because it diffusely infiltrates the gastric wall. SGC is associated with significant stromal proliferation and fibrosis and frequently causes peritoneal metastasis. The five-year survival rate is only around 10%, making it a refractory cancer with a poor prognosis, especially prevalent in Japan. In particular, patients with peritoneal metastasis have a mean survival of only a few months and they suffer from complications such as malignant ascites and intestinal obstruction, which substantially reduce QOL. The molecular mechanisms underlying the progression and peritoneal metastasis of SGC remain poorly understood, and no effective therapies have been established. Therefore, there is an urgent need to develop novel therapeutic strategies targeting the unique biological characteristics of SGC.
Our team has been working to elucidate the molecular mechanisms of invasion and peritoneal metastasis in SGC and to develop regulatory methods by employing phosphoproteomic analysis and studying cancer-stroma interactions. We have successfully identified multiple molecules involved in the peritoneal dissemination of SGC and obtained candidate antibodies and compounds that could serve as potential therapeutic agents. Recently, using multicolor fluorescent cell lineage tracing, we have been analyzing the clonality and mechanisms of peritoneal metastasis, yielding intriguing findings. In this seminar, I would like to present the results of these research projects. |
