MD Anderson 188bet体育网址Research Research亮点2022年5月4日

具有细胞疗法进展,新型免疫疗法和靶向疗法组合,新的肺癌靶标和乳腺癌差异

德克萨斯大学MD Anderson癌症中心的研究重点介绍了最近发表188bet体育网址的有关基本,转化和临床癌症研究的研究MD Andersonexperts. Studies include clinical advances with a new combination therapy targeting angiogenesis in platinum-resistant ovarian cancer and a promising immunotherapy combination for kidney cancer, plus laboratory studies that focus on targeting ferroptosis in specific lung cancers, developing chimeric antigen receptor (CAR) T cell therapies for blastic plasmacytoid dendritic cell neoplasms, and characterizing racial and ethnic disparities in breast cancer early detection.

Combination therapy targeting angiogenesis drivers demonstrates durable clinical activity in platinum-resistant ovarian cancer
Platinum resistance is often linked to a poor prognosis and occurs frequently in patients with advanced epithelialovarian cancer以前用铂基处理化学疗法. Targeting血管生成驱动因素(例如Delta样配体4(DLL4))可能会改善对血管内皮生长因子(VEGF)抑制剂的反应,并可能导致抗铂抗性卵巢癌(PROC)患者的结果改善。Siqing Fu, M.D., Ph.D., 和researchers evaluated the safety and efficacy of navicixizumab, which inhibits both VEGF and DLL4, in combination with paclitaxel in 44 patients with previously treated, recurrent, grade 2/3 PROC. The combination demonstrated promising clinical activity with manageable toxicity in both bevacizumab-treated and -naive patients. The overall objective response rate (ORR) was 43.2% in patients previously treated with bevacizumab, 64.3% in bevacizumab-naive patients, and 62% in patients with high angiogenesis or immune-suppressed tumor microenvironment subtypes. In patients previously treated with a PARP inhibitor, the ORR was 45%. The median duration of response was six months. The durable clinical activity of this combination suggests that navicixizumab may offer clinical benefits after other therapies for PROC, including bevacizumab, have been exhausted. Further Phase III evaluation of navicixizumab is planned. Learn more in the临床肿瘤学杂志.

Sitravatinib Plus Nivolumab显示出对晚期透明细胞肾细胞癌的希望
免疫检查点抑制剂已经为一些晚期清除细胞的患者提供了临床益处肾细胞癌(ccRCC), but many patients have limited responses to this treatment. This Phase I/II trial, led byPavlos Msaouel, M.D., Ph.D., 和Nizar Tannir,医学博士,测试了Sitravatinib的联合疗法 - 酪氨酸激酶抑制剂(TKI) - 加上42例在抗血管生成治疗后疾病进展后未接受免疫疗法的42例抗PD-1免疫疗法Nivolumab。设计,进行和分析了临床试验的免疫监测研究Sangeeta Goswami,医学博士,博士Padmanee Sharma,医学博士,博士Sitravatinib在肿瘤微环境中降低了免疫抑制性髓样细胞,导致35.7%的缓解率和中位无进展生存期为11.7个月。该组合没有意外毒性,在中位随访18.7个月后,有80.1%的患者还活着。此外,患有肝转移的患者表现出与没有肝转移的患者相当的耐用反应。这些结果支持进一步探索这种组合疗法,以改善晚期CCRCC中抗PD-1疗法的预后。了解更多信息科学翻译医学.

铁铁蛋白蛋白可能是新的治疗靶点KEAP1- 肺癌
铁凋亡是一种受控细胞死亡的铁依赖性形式,是由脂质过氧化物的有毒积累引起的 - 氧化形式的脂肪酸形式。靶向铁毒性可能是治疗癌症的可行策略,但是许多调节铁凋亡的机制仍然未知。在一项新的研究中,由Pranav188bet体育网址i Koppula博士,广告博士和博士学位的研究人员和Boyi Gan, Ph.D., discovered a novel approach to targeting ferroptosis in specific肺癌.KEAP1mutations, found in about 16% of non-small cell lung cancers, are associated with therapy resistance and poorer outcomes. The researchers identified ferroptosis suppressor protein 1 (FSP1) as a key regulator in this process. The team demonstrated that FSP1 acts downstream of KEAP1 and its target, NRF2, to process the antioxidant ubiquinone (CoQ). FSP1 promotes resistance to ferroptosis and放射治疗KEAP1- 突出癌细胞。靶向FSP1-COQ途径敏感Keap1-mutant lung cancers to radiation therapy by inducing ferroptosis, suggesting further studies are warranted to evaluate this as a therapeutic target. Learn more inNature Communications.

同种异体UCART123细胞显示在BPDCN临床前模型中的活性
乳质细胞类动物树突状细胞肿瘤(BPDCN)是一种罕见的白血病类型,与当前疗法的结局不佳有关。白介素3受体亚基α(CD123)在几乎所有BPDCN的情况下都过表达,这使其成为有吸引力的治疗靶标。在一项新研究中,研究人员领导188bet体育网址Marina Konopleva, M.D., Ph.D.,使用的UCART123是一种针对BPDCN细胞的健康供体细胞生产的基因修饰的同种异体T细胞产物。修饰的T细胞使用基因编辑技术表达抗CD123嵌合抗原受体(CAR)和TCRA常数(TRAC)基因。UCART123在实验室样品中消除了BPDCN,并在原发性患者衍生的BPDCN模型的子集中产生了长期无病生存。这些结果表明,同种异体UCART123细胞具有有效的抗BPDCN活性,并支持在未来的研究中评估该治疗方法。阅读更多信息Nature Communications.

早期乳腺癌检测和生存的种族和种族差异持续存在
乳腺癌筛查近几十年来,早期的探测工作已导致生存的提高乳腺癌在早期阶段更容易治疗。但是并非所有妇女都同样受益。一项由领导的研究Shine Chang,博士, 和Kristin Primm, Ph.D., used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER), examining 841,975 women who were diagnosed with breast cancer between 2000 and 2017. The study found that Black, American Indian, Southeast Asian, South Asian, Pacific Islander and Hispanic women were less likely than white women to be diagnosed with early-stage breast cancer. Among those with an early-stage diagnosis, Hispanic, American Indian, Pacific Islander and Black women were more likely than white women to die from breast cancer. For women with a late-stage diagnosis, the disparity was greatest for Black women, who had 18% higher mortality than white women. The findings emphasize the need for more work to reduce breast cancer disparities. Learn more inCancer Epidemiology, Biomarkers & Prevention.

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