A Selective and Powerful Small-Molecule Inhibitor to Stop Liver Cancer Spread 開啟肝癌新突破的小分子 CXCR4 抑制劑

Liver cancer often becomes life-threatening because cancer cells can migrate, invade other organs, and resist treatment. A key molecule that drives this behavior is CXCR4, a receptor that helps cancer cells move and survive in harsh, low-oxygen environments. We developed a highly selective and effective small-molecule CXCR4 inhibitor, called BPRCX807, designed to precisely block this pathway while minimizing unwanted side effects.

In liver cancer models, this targeted inhibitor significantly reduced tumor growth, prevented metastasis, and reshaped the tumor microenvironment to support stronger anti-cancer immune responses. Even more importantly, when combined with standard therapies like sorafenib or immune checkpoint inhibitors, it showed strong synergistic effects and extended survival. By precisely shutting down a key communication signal that cancer cells rely on, this small molecule offers a promising new strategy to control liver cancer more effectively and safely.

肝癌之所以危險，不只是因為腫瘤本身生長迅速，更因為癌細胞容易轉移並對治療產生抗性。其中一個關鍵分子是 CXCR4 受體，它幫助癌細胞遷移、在缺氧環境中存活，並塑造有利於腫瘤生長的免疫抑制環境。我們與國衛院生藥所夏克山研究員團隊共同開發了一種高度選擇性且效果優異的小分子 CXCR4 抑制劑，能精準阻斷這條關鍵訊號路徑，同時降低非特異性副作用。在肝癌動物模型中，這種抑制劑不僅顯著抑制腫瘤生長與遠端轉移，還改善腫瘤的免疫微環境。更重要的是，當它與現有的標靶治療或免疫治療合併使用時，能產生更強的協同效果並延長存活時間。透過精準關閉癌細胞依賴的重要訊號，小分子抑制劑為肝癌治療帶來新的可能性。（本研究成果榮獲未來科技獎, 國家新創獎）

A Highly Selective and Potent CXCR4 Antagonist for Hepatocellular Carcinoma Treatment.  Proc. Natl. Acad. Sci. U.S.A, 118 (13) e2015433118.