The University of Texas MD Anderson Cancer Center SPORE in Hepatocellular Carcinoma

德克萨斯大学 MD 安德森癌症中心 SPORE 在肝细胞癌中的应用

• 批准号: 10687031
• 负责人: LAURA BERETTA
• 金额: $ 220.67万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10687031
• 关键词: Address; Adjuvant; Affect; BAY 54-9085; Basic Science; Bile Acids; Biological Availability; Biological Markers; Cancer Center; Cancer Etiology; Catchment Area; Cells; Cessation of life; Chronic Disease; Cirrhosis; Clinical Trials; County; Curative Surgery; Data; Death Rate; Diabetes Mellitus; Diagnosis; Early Intervention; Excision; FDA approved; Fatty Acids; Fibrosis; Geography; Goals; Hispanic Populations; Immune; Immune Targeting; Immunotherapy; Incidence; Liver; Liver Fibrosis; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of thyroid; Measures; Mexico; Neoadjuvant Therapy; Newly Diagnosed; Nivolumab; Obesity; Operative Surgical Procedures; Oral; Participant; Patients; Performance; Pharmaceutical Preparations; Phosphorylation; Placebos; Plasma; Postoperative Period; Primary carcinoma of the liver cells; Prognosis; Prospective Studies; Prospective cohort; Proteins; Recurrence; Recurrent tumor; Resectable; Resected; Risk; STAT3 gene; Signal Transduction; South Texas; Survival Rate; Systemic Therapy; Target Populations; Texas; Therapeutic; Translational Research; Tyrosine Kinase Inhibitor; Underserved Population; United States; University of Texas M D Anderson Cancer Center; advanced disease; anti-PD-1; anti-tumor immune response; antitumor effect; arm; biobank; biomarker development; cancer diagnosis; cancer site; care seeking; checkpoint therapy; chronic liver disease; diabetic; elastography; gut microbiome; immune checkpoint; immunoregulation; improved; improved outcome; inhibitor; innovation; liver biopsy; liver injury; liver transplantation; mortality; non-alcoholic; nonalcoholic steatohepatitis; patient population; prognostic significance; programmed cell death ligand 1; response; screening; trend; tumor; tumor behavior; tumor growth; vibration

Overall - SUMMARY/ABSTRACT The overall goal of the University of Texas MD Anderson Cancer Center SPORE in Hepatocellular Carcinoma (HCC) is to improve outcomes for HCC patients and reduce the mortality rates of HCC through early intervention. HCC is the 2nd leading cause of cancer death worldwide with 854,000 new cases diagnosed globally and 810,000 deaths in 2015. The incidence of new HCC cases globally is projected to rise to 1,341,344 cases by 2035. In the United States (U.S.), while death rates declined for all cancers combined and for most cancer sites in the past 10 years, deaths from HCC increased at the highest rate of all cancer sites, and HCC incidence rates increased sharply, second only to thyroid cancer. The burden of HCC is not equally distributed throughout the U.S., the highest incidence being observed in States on the Mexico-US Border. Texas ranks second in incidence of HCC, with a 5-year rate of 11.4 cases per 100,000 compared to the nation rate of 7.6. Within Texas, Hispanics in counties bordering Mexico have the highest rates of HCC in the U.S., with 37.5 diagnosed cases per 100,000. Reflecting the rising incidence trends, the number of HCC patients seeking care at MD Anderson Cancer Center has increased every year, from 277 patients in 2013 to 580 patients in 2017, a 2-fold increase over the most recent 5 years. The relative 5-year survival rate for HCC is 16%. The poor prognosis of HCC is due to multiple factors: 1) the vast majority of HCC cases are diagnosed at an advanced stage, not amenable to curative surgical treatment (resection or liver transplantation); 2) even resected cases suffer from high rates of recurrence (up to 50% in 2 years and 70% in 5 years); 3) HCC often occurs in the context of advanced chronic liver disease, cirrhosis in particular, limiting treatment options; 4) the only FDA-approved first line systemic therapy is sorafenib which offers a 2.8 months improvement in overall survival and a dismal response rate of 2%; and 5) the recently approved second line therapy are another tyrosine kinase inhibitor regorafenib and the immunotherapy drug nivolumab, but again improvement in overall survival and response rates are very low. In this SPORE application, 3 projects together with 3 cores will: 1) evaluate the effect of checkpoint therapy in neoadjuvant and adjuvant HCC settings and determine optimal combinations with checkpoint therapeutics to enhance the anti-tumor immune response; 2) determine the prognostic significance of phosphorylated STAT3 as a biomarker for postoperative recurrence and evaluate TTI-101 (C188-9), a STAT3 inhibitor developed in-house, as a post-operative adjuvant; 3) evaluate the combination of nivolumab and TTI-101 in the treatment of patients with advanced stage HCC; 4) perform extensive screening for liver fibrosis in obese and diabetic Hispanics in South Texas, and identify non-invasive biomarkers of fibrosis stage and progression in this underserved population highly affected by non-alcoholic steatohepatitis and HCC.

总体 - 摘要/摘要 德克萨斯大学 MD 安德森癌症中心 SPORE 在肝细胞癌方面的总体目标 （HCC）旨在通过早期治疗来改善 HCC 患者的预后并降低 HCC 的死亡率 干涉。 HCC 是全球第二大癌症死亡原因，新诊断病例达 854,000 例 全球范围内，2015 年有 810,000 人死亡。全球新发 HCC 病例的发生率预计将上升至 到 2035 年，这一数字将达到 1,341,344 例。在美国，虽然所有癌症的死亡率合计有所下降， 在过去 10 年中，对于大多数癌症部位来说，HCC 死亡人数的增幅是所有癌症部位中最高的， 肝癌发病率急剧上升，仅次于甲状腺癌。 HCC 的负担并不相同 分布于美国各地，其中墨西哥-美国边境各州的发病率最高。 德克萨斯州的 HCC 发病率排名第二，与全国相比，五年发病率为每 10 万人 11.4 例 率为7.6。在德克萨斯州，与墨西哥接壤的县的西班牙裔美国人的肝癌发病率最高， 每10万确诊病例为37.5例。 HCC 患者数量反映了发病率上升的趋势 到 MD 安德森癌症中心寻求治疗的患者逐年增加，从 2013 年的 277 名患者增加到 580 名患者 2017年患者数量比最近5年增加了2倍。 HCC 的相对 5 年生存率为 16%。 HCC 的预后不良是由多种因素造成的：1）绝大多数 HCC 病例是在 晚期，不适合根治性手术治疗（切除或肝移植）； 2）均匀 切除病例复发率高（2年可达50%，5年可达70%）； 3) 经常发生肝癌 发生在晚期慢性肝病，特别是肝硬化的背景下，限制了治疗选择； 4） 唯一获得 FDA 批准的一线全身治疗药物是索拉非尼，它使总体症状改善了 2.8 个月 存活率和 2% 的低反应率； 5) 最近批准的二线疗法是另一种 酪氨酸激酶抑制剂瑞戈非尼和免疫治疗药物纳武单抗，但总体再次改善 存活率和缓解率非常低。在此 SPORE 应用程序中，3 个项目和 3 个核心将：1) 评估检查点治疗在新辅助和辅助 HCC 设置中的效果并确定最佳方案 与检查点疗法相结合，增强抗肿瘤免疫反应； 2）确定 磷酸化STAT3作为术后复发生物标志物的预后意义及评估 TTI-101 (C188-9)，一种内部开发的 STAT3 抑制剂，作为术后辅助剂； 3）评估 nivolumab 与 TTI-101 联合治疗晚期 HCC 患者； 4）执行 对德克萨斯州南部肥胖和糖尿病西班牙裔人的肝纤维化进行广泛筛查，并确定非侵入性治疗方法 在这一服务不足的人群中，纤维化阶段和进展的生物标志物深受非酒精饮料的影响 脂肪性肝炎和肝癌。

项目成果

Radiomics, deep learning and early diagnosis in oncology.

放射组学、深度学习和肿瘤学早期诊断。

• 发表时间: 2021-12-21
• 作者: Wei; Peng
• 通讯作者: Peng

Plasma Growth Hormone as a Prognostic Biomarker to Durvalumab and Tremelimumab in Patients with Advanced Hepatocellular Carcinoma.

血浆生长激素作为晚期肝细胞癌患者 Durvalumab 和 Tremelimumab 的预后生物标志物。

• 发表时间: 2024
• 作者: Chamseddine, Shadi;LaPelusa, Michael;Xiao, Lianchun;Mohamed, Yehia I;Lee, Sunyoung S;Hu, Zishuo Ian;Hatia, Rikita I;Hassan, Manal;Yao, James C;Duda, Dan G;Datar, Saumil;Amin, Hesham M;Kaseb, Ahmed O
• 通讯作者: Kaseb, Ahmed O

Effect of sarcopenia on systemic targeted therapy response in patients with advanced hepatocellular carcinoma.

肌肉减少症对晚期肝细胞癌患者全身靶向治疗反应的影响。

• 发表时间: 2021-03
• 作者: Qayyum, Aliya;Bhosale, Priya;Aslam, Rizwan;Avritscher, Rony;Ma, Jingfei;Pagel, Mark D;Sun, Jia;Mohamed, Yehia;Rashid, Asif;Beretta, Laura;Kaseb, Ahmed O
• 通讯作者: Kaseb, Ahmed O

Dietary Patterns and Hepatocellular Carcinoma Risk among US Adults.

美国成年人的饮食模式和肝细胞癌风险。

• 发表时间: 2021-06-11
• 影响因子: 5.9
• 作者: Moussa, Iman;Day, Rena S;Li, Ruosha;Du, Xianglin L;Kaseb, Ahmed O;Jalal, Prasun K;Daniel;Hatia, Rikita I;Abdelhakeem, Ahmed;Rashid, Asif;Chun, Yun Shin;Li, Donghui;Hassan, Manal M
• 通讯作者: Hassan, Manal M

Pediatric combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features: distinguishing genetic alterations detected by chromosomal microarray.

具有神经内分泌特征的儿科联合肝细胞胆管癌（cHCC-CC）：通过染色体微阵列检测到的区分遗传改变。

• 发表时间: 2023-02-13
• 影响因子: 2.6
• 作者: Wilhelm, Alyeesha B;Cunningham, Arwyn G;Kassab, Cynthia;Fitz, Eric C;Dong, Jianli;Radhakrishnan, Ravi S;Ranganathan, Sarangarajan;Tan, Dongfeng;Stevenson, Heather L
• 通讯作者: Stevenson, Heather L