查看狗狗血管肉瘤作为人类血管肉瘤药物探索研究的潜力非啮齿动物模型的源代码
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狗狗血管肉瘤作为人类血管肉瘤药物探索研究的潜力非啮齿动物模型
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== 其他治疗方案和潜在治疗方法正在研究中 == Other treatment options and potential treatment under investigation 对于人类 AS 的治疗,已经探索了几种靶向药物作为替代选择。已经评估了靶向 VEGF-VEGFR 血管生成通路的药物用于肉瘤,包括贝伐珠单抗和帕唑帕尼。贝伐珠单抗是一种靶向 VEGFA 的单克隆抗体 (84, 100, 101),在一项 II 期临床试验中,23 名患者中只有 2 名表现出部分缓解,23 名患者中有 11 名病情稳定 (84)。考虑到 AS 中众所周知的 VEGFA-VEGFR 通路的改变,结果令人失望。酪氨酸激酶抑制剂帕唑帕尼也产生了适度的结果,中位无进展生存期 (PFS) 为 3 个月,在一项回顾性研究中没有显著反应 (102)。免疫检查点抑制剂 (ICI) 最近成为 AS 的另一种选择。抗 PD1(程序性死亡 1)检查点抑制剂 pembrolizumab 被批准用于具有高肿瘤突变负荷的肿瘤,无论组织学如何 (103)。帕博利珠单抗对标准疗法难治的转移性 AS 病例中有 2 例表现出特殊和持久的反应[64]。尽管需要进一步的研究来证实其疗效,但这些报告表明 ICI 在 AS 治疗方面具有广阔的潜力。 对于犬 HSA,已探索多种药物作为替代选择,包括靶向 KDR 的酪氨酸激酶抑制剂 ('''Toceranib''')(90)、基于紫杉烷的药物 ('''Paccal-Vet''') (104)、'''免疫检查点抑制剂''' (ICI) (105, 106)、其他形式的蒽环类药物(表柔比星)(107)、聚乙二醇化脂质体包封的多柔比星 (108)、'''COX-2 抑制剂''' (109) 和'''沙利度胺''' (110)。Toceranib 是一种靶向 KDR 的酪氨酸激酶抑制剂 (90),已被探索用于治疗犬 HSA。然而,结果令人失望:一项前瞻性研究表明,在基于多柔比星的化疗后使用托塞拉尼 (Toceranib) 并未改善 I 期或 II 期犬 HSA 的无病间隔或 OS(中位无病间隔,161 天。中位生存时间,172 天)(90)。Paccal Vet 是一种水溶性紫杉醇胶束制剂,已被研究用于治疗犬 HSA。紫杉醇尚未用于狗,因为静脉内给予时超敏反应的发生率很高(111,112)。然而,Paccal Vet 旨在不诱导这种超敏反应,因此预计它可用于治疗犬 HSA (104)。尽管 ICI 尚未用于狗的市售,但第一种抗犬 PD-1 抗体 '''Gilvetmab''' 已于 2023 年 10 月获得批准(美国默克动物健康中心)。目前,Gilvetmab 仅获批用于 2 种肿瘤类型(肥大细胞瘤和恶性黑色素瘤),其对犬 HSA 的临床疗效尚不清楚。尽管需要进一步研究,但 ICI 作为犬 HSA 的治疗方式与人类 AS 一样具有广阔的潜力。还有一些其他形式的常规免疫疗法,比如 HSA 疫苗 (113)、脂质体封装的胞壁酰三肽磷脂酰乙醇胺 (LMTP-PE) (114) 和多糖肽 (polysaccharopeptide)(115),然而,它们的疗效可能有限。 For the treatment of human AS, several targeted agents have been explored as alternative options. Agents targeting the VEGF-VEGFR angiogenic pathway have been assessed for sarcoma, including bevacizumab and pazopanib. Bevacizumab, a monoclonal antibody targeting VEGFA (84, 100, 101), produced modest results with only 2 out of 23 patients showing a partial response and 11 out of 23 patients with stable disease in a Phase II clinical trial (84). The results were disappointing considering the well-known alteration of the VEGFA-VEGFR pathway in AS. Pazopanib, a tyrosine kinase inhibitor, also yielded modest results with a median progression-free survival (PFS) of 3 months and no significant responses in a retrospective study (102). Immune checkpoint inhibitors (ICIs) have recently emerged as another option for AS. The anti-PD1 (programmed death 1) checkpoint inhibitor pembrolizumab was approved for tumors with a high tumor mutation burden regardless of histology (103). Pembrolizumab showed an exceptional and durable response to 2 out of 3 metastatic AS cases that were refractory to standard therapies (64). Although further studies are required to confirm their efficacy, these reports suggest the promising potential of ICIs for AS treatment. For canine HSA, multiple agents have been explored as alternative options, including a tyrosine kinase inhibitor targeting KDR (toceranib) (90), a taxane-based agent (Paccal-Vet) (104), immune checkpoint inhibitors (ICIs) (105, 106), other forms of anthracycline (epirubicin) (107), pegylated liposome-encapsulated doxorubicin (108), COX-2 inhibitors (109), and thalidomide (110). Toceranib, a tyrosine kinase inhibitor targeting KDR (90), has been explored for the treatment of canine HSA; however, the results were disappointing: a prospective study showed that the use of toceranib following doxorubicin-based chemotherapy did not improve either disease-free interval or OS in stage I or II canine HSA (a median disease-free interval, 161 days; a median survival time, 172 days) (90). Paccal Vet, a water-soluble, micellar formulation of paclitaxel, has been investigated for treating canine HSA. Paclitaxel has not been used in dogs due to high rates of hypersensitivity reactions when given intravenously (111, 112); however, Paccal Vet is designed not to induce such hypersensitivity, thus it is expected to be useful for the treatment of canine HSA (104). Although ICIs had not been commercially available for dogs, Gilvetmab, the first anti-canine PD-1 antibody, has been approved in October 2023 (Merck Animal Health USA). Currently, Gilvetmab is approved only for 2 tumor types (mast cell tumor and malignant melanoma), and its clinical efficacy for canine HSA is still unclear. Although further studies are required, ICIs have promising potential as a therapeutic modality for canine HSA as in human AS. Several other forms of conventional immunotherapy are documented, including an HSA vaccine (113), liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (LMTP-PE) (114), and polysaccharopeptide (115); however, their efficacy may be limited. <br>
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