Systemic therapies for salivary gland adenoid cystic carcinoma

被引:11
|
作者
Sahara, Sosuke [1 ,2 ]
Herzog, Alexandra E. [1 ]
Nor, Jacques E. [1 ,3 ,4 ,5 ]
机构
[1] Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
[2] Hamamatsu Univ Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Hamamatsu, Shizuoka 4313192, Japan
[3] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Sch Med, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Biomed Engn, Coll Engn, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA
来源
AMERICAN JOURNAL OF CANCER RESEARCH | 2021年 / 11卷 / 09期
关键词
Adenoid cystic carcinoma; cancer stem cells; systemic therapy; chemotherapy; immunotherapy; sali-vary gland cancer; CANCER STEM-CELLS; PHASE-II TRIAL; ENDOTHELIAL-GROWTH-FACTOR; CISPLATIN COMBINATION CHEMOTHERAPY; VINORELBINE PLUS CISPLATIN; RNA-BASED ADJUVANT; FACTOR RECEPTOR; C-KIT; MEDIATED-IMMUNITY; CLINICAL-TRIAL;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adenoid cystic carcinoma (ACC) is a slow growing, but relentless cancer. Due to its rarity and lack of understanding of its molecular etiology, no standard chemotherapy for ACC currently exists and many patients suffer from recurrent and/or metastatic disease. As such, development of safe and effective therapies is imperative. To describe and summarize existing clinical trial studies and preclinical discoveries, we surveyed the PubMed on developmental therapeutics for ACC. Objective response rates to monotherapy with cytotoxic agents were approximately 10% with cisplatin, 5-FU, gemcitabine, mitoxantrone, epirubicin, vinorelbine and paclitaxel. The most studied combination therapies were cyclophosphamide-doxorubicin-cisplatin (CAP) and cisplatin-vinorelbine, with an objective response rate of 18-31%. Among molecularly targeted drugs, the most studied drugs are inhibitors targeting the vascular endothelial growth factor receptor (VEGFR) to inhibit tumor angiogenesis. Among those, lenvatinib and axitinib showed a relatively high objective response rate of 11-16% and 9-17%, respectively. Given high recurrence rates and chemoresistance of ACC, treatments targeting cancer stem cells (CSC), which function as tumor-initiating cells and drive chemoresistance, may be particularly valuable. CSC have been shown to be targetable via MYB, Notch1, p53 and epigenetic mechanisms. Myb overexpression is characteristic in ACC but was previously thought to present a difficult target due to its nature as a transcription factor. However, due to the development Myb-targeted inhibitors and an ongoing clinical trial of MYB-targeted cancer vaccine therapy, MYB is becoming an increasingly attractive therapeutic target. Drugs targeting NOTCH signaling demonstrated 5-17% response rate in phase I clinical trials. Within the field of epigenetics, treatment with PRMT5 inhibitors has shown 21% partial response rate in phase I clinical trial. Immunotherapies, such as PD-1 inhibitors, are also associated with CSC, but have not been effective against ACC. However, clinical trials of cancer vaccine therapies are actively being conducted. In addition to conventional chemotherapies and inhibitors of angiogenesis, the emergence of new therapies such as immunotherapy and those targeting cancer stemness is expected to bring clinical benefits to patients in the future.
引用
收藏
页码:4092 / 4110
页数:19
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