Pan-Chyr Yang
Affiliations
President and Professor, National Taiwan University
Biography
Dr. Yang currently is the President of National Taiwan University and Professor in the Department of Internal Medicine, National Taiwan University College of Medicine. His major research interests are pulmonary and critical care medicine, molecular and cellular biology, lung cancer genomics and personalized cancer therapy. He was elected member of Academia Sinica in 2006 because of his contributions in leading the translational research and implementation of precision therapy for lung cancer in Taiwan, which have significantly improved the survival in lung cancer patients.
His research group identified novel genes and pathways that associated with lung cancer progression. They established new platform for development of lung cancer stem cell directed therapy and discovered the autocrine-paracrine interaction between the lung cancer stem cell with cancer microenvironment. They also identified specific gene expression and microRNA biomarkers that might be beneficial for personalized therapy of lung cancer patients.
Abstract
Cancer stem cell directed therapy for lung cancer
Pan-Chtr Yang, MD, PhD
Cancer stem cells (CSCs) are believed to be the cause and initiation of most malignant tumours. The CSCs can interact with tumor microenvironment or niche and play critical roles in cancer recurrence, metastasis and drug resistance. The CSCs are one of the major therapeutic targets for treating cancer. However, how CSC interacts with tumor microenvironment and maintains its plasticity is unclear. We have established a sustainable primary culture of Oct3/4(+)/Nanog(+) lung CSCs fed with CD90(+) cancer-associated-fibroblasts (CAFs) from non-small cell lung cancer (NSCLC) patients.
The transcriptomic analysis identified paracrine-network on the tumor microenvironment supports that enriches CSCs through dedifferentiation and reacquisition of stem-cell-like properties. We showed that IGF1R signaling activation in CSCs in the presence of CAFs. The CAFs could express IGF-II that induce Nanog expression in CSCs and promote cancer stemness. Moreover, the biomarkers derived from this paracrine signaling predict overall and relapse-free survival in stage-I NSCLC patients. We further showed that IGF-II/IGF1R signaling blockade could inhibit Nanog expression in CSCs and attenuates cancer stemness. Our results support that CAFs constitute the critical supporting niche for cancer stemness. The CSC/microenvironment-directed therapy is a potential new therapeutic strategy for lung cancer patients.
