生物标志物指导癌症患者个体化治疗的策略有助于提高癌症患者的整体疗效。课题组在揭示内源性生长分化因子15(GDF15)促进口腔鳞癌发生发展分子机制、口腔鳞癌TPF诱导化疗三期临床试验中高表达GDF15的cT3/4N0M0患者能从诱导化疗生存获益的基础上，发现erbB2可能作为内源性GDF15结合蛋白调控PI3K/MAPK信号通路、外源性GDF15可能抑制口腔鳞癌细胞增殖。本项目旨在开展口腔鳞癌GDF15分子、细胞生物学的分子机制和临床试验样本研究，重点围绕内源性GDF15如何通过erbB2调控相关信号通路，为其他高表达GDF15口腔鳞癌患者寻求新的治疗方案，外源性重组GDF15能否成为提高口腔鳞癌治疗效果的靶点，阐明不同形式GDF15在口腔鳞癌中的生物学功能，完善GDF15在口腔鳞癌治疗中的分子机制体系，为实现GDF15作为生物标志物指导口腔鳞癌个体化治疗的转化研究提供科学依据。

Biomarker-based personalized therapeutic research strategies are expected to improve overall clinical outcomes in cancer patients. The key point of realizing biomarker-based personalized treatment in patients with oral squamous cell carcinoma (OSCC) is to screen the proper patients who might benefit from the proper treatment on the basis of biomarker detection. Our previous studies have found that endogenous growth differentiation factor 15 (GDF15) played an important role in promoting the development of OSCC from the perspective of molecular mechanism on AKT/ERK pathway, the OSCC patients at clinical stage T3/4N0M0 and with GDF15 overexpression could benefit from TPF induction chemotherapy in clinical survival, who came from our finished phase III clinical trial (NCT01542931) that investigated the potential survival benefit of adding TPF (docetaxel, cisplatin and 5-fluorouracil) induction chemotherapy before standard treatment of surgery and radiotherapy in patients with locally advanced OSCC comparing to the standard treatment. Recently, our initial experiments found that erbB2, not AKT or ERK, may act as an endogenous GDF15 binding protein to regulate the PI3K/MAPK signal pathway; exogenous recombinant GDF15 could inhibit the cell proliferation in OSCC. However, in the literatures, there are few studies reporting the molecular mechanism of endogenous GDF15 expression on erbB2 pathways in OSCC, there are either few studies reporting the mechanism of exogenous GDF15 in OSCC treatment; therefore, there are still a lot of unknown mechanisms to be further investigated. Our present study will combine the basic mechanism and clinical investigations to reveal the molecular mechanism of endogenous GDF15 regulating related signal pathway via erbB2 to explore the potential treatment protocol for the patients with GDF15 overexpression but could not benefit from TPF induction chemotherapy; and reveal the molecular mechanism of exogenous GDF15 as a potential target in OSCC treatment. The aim of this study is to clarify the biological functions of different types of GDF15 in OSCC, to better understand the system of molecular mechanism of GDF15 in OSCC treatment, to provide scientific evidence for translational research on GDF15 as a predictive biomarker for personalized treatment strategy in OSCC.