Systemic therapies for salivary gland adenoid cystic carcinoma
被引:11
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作者:
Sahara, Sosuke
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机构:
Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
Hamamatsu Univ Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Hamamatsu, Shizuoka 4313192, JapanUniv Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
Sahara, Sosuke
[1
,2
]
Herzog, Alexandra E.
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机构:
Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USAUniv Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
Herzog, Alexandra E.
[1
]
Nor, Jacques E.
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机构:
Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Otolaryngol Head & Neck Surg, Sch Med, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Biomed Engn, Coll Engn, Ann Arbor, MI 48109 USA
Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USAUniv Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
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
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.
机构:
Woodland Hills Med Ctr, Dept Pathol, So Calif Permanente Med Grp, Woodland Hills, CA 90015 USAWoodland Hills Med Ctr, Dept Pathol, So Calif Permanente Med Grp, Woodland Hills, CA 90015 USA
机构:
Johns Hopkins Univ Hosp, Dept Pathol, Div Cytopathol, Baltimore, MD 21287 USA
Chiang Mai Univ, Fac Med, Dept Pathol, Chiang Mai, ThailandJohns Hopkins Univ Hosp, Dept Pathol, Div Cytopathol, Baltimore, MD 21287 USA
Chowsilpa, Sayanan
An, Daniel
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机构:
Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USAJohns Hopkins Univ Hosp, Dept Pathol, Div Cytopathol, Baltimore, MD 21287 USA
An, Daniel
Maleki, Zahra
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机构:
Johns Hopkins Univ Hosp, Dept Pathol, Div Cytopathol, Baltimore, MD 21287 USAJohns Hopkins Univ Hosp, Dept Pathol, Div Cytopathol, Baltimore, MD 21287 USA
机构:
Univ Chicago, Pritzker Sch Med, 924 57th St Suite 104, Chicago, IL 60637 USAUniv Chicago, Pritzker Sch Med, 924 57th St Suite 104, Chicago, IL 60637 USA
Kacew, Alec J. J.
Hanna, Glenn J. J.
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机构:
Dana Farber Canc Inst, Ctr Head & Neck Oncol, Ctr Salivary & Rare Head & Neck Canc, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USAUniv Chicago, Pritzker Sch Med, 924 57th St Suite 104, Chicago, IL 60637 USA