Cytotoxic and targeted therapy for BRCA1/2-driven cancers.

IF 2 4区 医学 Q3 ONCOLOGY Hereditary Cancer in Clinical Practice Pub Date : 2021-08-28 DOI:10.1186/s13053-021-00193-y
Evgeny N Imyanitov
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引用次数: 7

Abstract

Tumors arising in BRCA1/2 germline mutation carriers usually demonstrate somatic loss of the remaining BRCA1/2 allele and increased sensitivity to platinum compounds, anthracyclines, mitomycin C and poly (ADP-ribose) polymerase inhibitors (PARPi). Exposure to conventional platinum-based therapy or PARPi results in the restoration of BRCA1/2 function and development of resistance to systemic therapy, therefore, there is a need for other treatment options. Some studies suggested that the use of specific drug combinations or administration of high-dose chemotherapy may result in pronounced tumor responses. BRCA1/2-driven tumors are characterized by increased immunogenicity; promising efficacy of immune therapy has been demonstrated in a number of preclinical and clinical investigations. There are outstanding issues, which require further consideration. Platinum compounds and PARPi have very similar mode of antitumor action and are likely to render cross-resistance to each other, so their optimal position in cancer treatment schemes may be a subject of additional studies. Sporadic tumors with somatically acquired inactivation of BRCA1/2 or related genes resemble hereditary neoplasms with regard to the spectrum of drug sensitivity; the development of user-friendly BRCAness tests presents a challenge. Many therapeutic decisions are now based on the BRCA1/2 status, so the significant reduction of the turn-around time for predictive laboratory assays is of particular importance.

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brca1 /2驱动癌症的细胞毒性和靶向治疗。
BRCA1/2种系突变携带者产生的肿瘤通常表现为剩余BRCA1/2等位基因的体细胞缺失,对铂类化合物、蒽环类药物、丝裂霉素C和聚(adp -核糖)聚合酶抑制剂(PARPi)的敏感性增加。暴露于常规铂基治疗或PARPi可导致BRCA1/2功能恢复并对全身治疗产生耐药性,因此需要其他治疗方案。一些研究表明,使用特定的药物组合或给予大剂量化疗可能导致明显的肿瘤反应。brca1 /2驱动的肿瘤以免疫原性增强为特征;许多临床前和临床研究已经证明了免疫治疗的良好疗效。还有一些悬而未决的问题需要进一步考虑。铂类化合物和PARPi具有非常相似的抗肿瘤作用模式,并且可能相互产生交叉抗性,因此它们在癌症治疗方案中的最佳位置可能是一个进一步研究的主题。BRCA1/2或相关基因体获得性失活的散发性肿瘤在药物敏感性谱方面与遗传性肿瘤相似;开发用户友好的BRCAness测试提出了一个挑战。现在许多治疗决定都是基于BRCA1/2的状态,因此显著减少预测实验室分析的周转时间是特别重要的。
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来源期刊
CiteScore
3.10
自引率
5.90%
发文量
38
审稿时长
>12 weeks
期刊介绍: Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.
期刊最新文献
BRCA2 germline mutation carrier with five malignancies: a case report. A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives. Breast cancer and ATM mutations: treatment implications. Meeting abstracts from the Annual Conference "Clinical Genetics of Cancer 2023". Validation of a guidelines-based digital tool to assess the need for germline cancer genetic testing.
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