Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing.
Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing.
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DOI：
10.1038/s41698-023-00379-8
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发表时间：
2023-05-18
影响因子：
7.9
通讯作者：
中科院分区：
文献类型：
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作者：
低级别浆液性卵巢癌（LGSOC）通常对标准铂类化疗反应较差，需要新的治疗方法。我们描述了一个铂类耐药的晚期LGSOC患者对靶向治疗的显著反应，该患者的标准治疗化疗和两次手术均失败。患者病情迅速下降，进入临终关怀家庭静脉（i. v.）阿片类镇痛药和需要G管的恶性肠梗阻对患者肿瘤的基因组分析没有显示出明显的治疗选择。相比之下，CLIA认证的患者肿瘤类器官培养物的药物敏感性试验确定了几种治疗选择，包括布鲁顿酪氨酸激酶（BTK）抑制剂伊曲替尼，以及EGFR抑制剂阿法替尼和厄洛替尼。在标签外每日给予伊曲替尼作为单药治疗后，患者在接下来的65周内出现了异常的临床转变，CA-125水平正常化，恶性肠梗阻消退，停止止痛药，体能状态从ECOG 3改善至ECOG 1。疾病稳定65周后，患者的CA-125水平开始升高，此时患者停用伊曲替尼并开始接受阿法替尼单药治疗。患者的CA-125水平在另外38周内保持稳定，但由于贫血和CA-125水平升高，患者改用厄洛替尼，目前正在监测。该病例突出了患者源性肿瘤类器官的体外药物测试的临床实用性，作为一种新的功能性精准医学方法，为标准治疗失败的患者确定有效的个性化治疗。
Low-grade serous ovarian cancer (LGSOC) typically responds poorly to standard platinum-based chemotherapy and new therapeutic approaches are needed. We describe a remarkable response to targeted therapy in a patient with platinum-resistant, advanced LGSOC who had failed standard-of-care chemotherapy and two surgeries. The patient was in rapid decline and entering hospice care on home intravenous (i.v.) opioid analgesics and a malignant bowel obstruction requiring a G-tube. Genomic analysis of the patient’s tumor did not indicate obvious therapeutic options. In contrast, a CLIA-certified drug sensitivity assay of an organoid culture derived from the patient’s tumor identified several therapeutic choices, including Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, as well as the EGFR inhibitors afatinib and erlotinib. Following off-label administration of daily ibrutinib as monotherapy, the patient had an exceptional clinical turnaround over the following 65 weeks with normalization of CA-125 levels, resolution of the malignant bowel obstruction, halting of pain medications, and improvement of performance status from ECOG 3 to ECOG 1. After 65 weeks of stable disease, the patient’s CA-125 levels began to rise, at which point the patient discontinued ibrutinib and began taking afatinib as monotherapy. The patient’s CA-125 levels remained stable for an additional 38 weeks but due to anemia and rising CA-125 levels, the patient switched to erlotinib and is currently being monitored. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new functional precision medicine approach to identify effective personalized therapies for patients who have failed standard-of-care treatments.
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影响因子：
28.2
作者：
Pauli C;Hopkins BD;Prandi D;Shaw R;Fedrizzi T;Sboner A;Sailer V;Augello M;Puca L;Rosati R;McNary TJ;Churakova Y;Cheung C;Triscott J;Pisapia D;Rao R;Mosquera JM;Robinson B;Faltas BM;Emerling BE;Gadi VK;Bernard B;Elemento O;Beltran H;Demichelis F;Kemp CJ;Grandori C;Cantley LC;Rubin MA
通讯作者：
Rubin MA
DOI：
10.1158/1078-0432.ccr-20-0073
发表时间：
2020-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Narasimhan V;Wright JA;Churchill M;Wang T;Rosati R;Lannagan TRM;Vrbanac L;Richardson AB;Kobayashi H;Price T;Tye GXY;Marker J;Hewett PJ;Flood MP;Pereira S;Whitney GA;Michael M;Tie J;Mukherjee S;Grandori C;Heriot AG;Worthley DL;Ramsay RG;Woods SL
通讯作者：
Woods SL
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
3.5
作者：
Hong, David;Rasco, Drew;Borazanci, Erkut
通讯作者：
Borazanci, Erkut
患者衍生的类器官为罕见的前列腺癌表型建模。
影响因子：
16.6
作者：
Puca L;Bareja R;Prandi D;Shaw R;Benelli M;Karthaus WR;Hess J;Sigouros M;Donoghue A;Kossai M;Gao D;Cyrta J;Sailer V;Vosoughi A;Pauli C;Churakova Y;Cheung C;Deonarine LD;McNary TJ;Rosati R;Tagawa ST;Nanus DM;Mosquera JM;Sawyers CL;Chen Y;Inghirami G;Rao RA;Grandori C;Elemento O;Sboner A;Demichelis F;Rubin MA;Beltran H
通讯作者：
Beltran H