Abstract 2568: Use of kinase inhibitors in Fanconi anemia oral cancercell lines

W. N. Jungbauer, Mustafa M. Ali, B. Wuertz, F. Ondrey
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引用次数: 1

Abstract

Successful Fanconi anemia (FA) treatment allows greater longevity for these patients. However, there is a greatly increased risk of squamous malignancies of the head and neck which are quite deadly in these young patients. There is an unmet need for non DNA damaging therapies for this malignancy which could augment surgery. Our approach has been to examine potential treatments based on known pathophysiology of the disease which would be acceptable for this population so we examined the effects of metformin and pioglitazone, as well as two cell cycle kinase inhibitors, in FA and leukoplakia cell lines. We examined dose-dependent and combination effects on cell proliferation, as judged by MTT assay. We examined metformin, pioglitazone, the polo-like kinase 1 inhibitor, GSK461364, and Wee1 kinase inhibitor, AZD1775.In single agent studies, we observed dose-dependent decreases in cell proliferation with all 4 single agents. We observed decreased cell proliferation in all cell lines at 72 hours at clinically achievable serum levels of 85% to 55% of control levels (P Citation Format: Walter N. Jungbauer, Mustafa M. Ali, Beverly R. Wuertz, Frank G. Ondrey. Use of kinase inhibitors in Fanconi anemia oral cancercell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2568.
2568:激酶抑制剂在范可尼贫血口腔癌细胞系中的应用
成功的范可尼贫血(FA)治疗可以延长这些患者的寿命。然而,头颈部鳞状恶性肿瘤的风险大大增加,这在这些年轻患者中是相当致命的。对这种恶性肿瘤的非DNA损伤治疗的需求尚未得到满足,这可能会增加手术。我们的方法是根据已知的疾病病理生理学来检查潜在的治疗方法,这对这个人群来说是可以接受的,所以我们检查了二甲双胍和吡格列酮,以及两种细胞周期激酶抑制剂对FA和白斑细胞系的影响。通过MTT试验,我们检测了剂量依赖性和联合作用对细胞增殖的影响。我们检测了二甲双胍、吡格列酮、polo样激酶1抑制剂GSK461364和Wee1激酶抑制剂AZD1775。在单药研究中,我们观察到所有4种单药对细胞增殖的剂量依赖性降低。我们观察到,在临床可达到的血清水平为对照水平的85%至55%的情况下,所有细胞系在72小时内的细胞增殖均下降(P引用格式:Walter N. Jungbauer, Mustafa M. Ali, Beverly R. Wuertz, Frank G. Ondrey)。激酶抑制剂在范可尼贫血口腔癌细胞系中的应用[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要第2568期。
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