Tan Joshua Zhi Chien, Zhang Zewen, Goh Hui Xuan, Ngeow Joanne
Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore 168583, Singapore.
Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore 168583, Singapore.
Cancers (Basel). 2024 Dec 24;17(1):8. doi: 10.3390/cancers17010008.
Identifying patients with gm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management. This review examines the evidence for the latest predictive and therapeutic approaches in -associated cancers.
Data supports the use of adjuvant olaparib in patients with gm high-risk HER2-negative breast cancer. In advanced gm HER2-negative breast cancer, the PARPis talazoparib and olaparib have demonstrated benefit over standard chemotherapy. In ovarian cancer, olaparib, niraparib or rucaparib can be used as monotherapy in frontline maintenance. Olaparib and bevacizumab as a combination can also be used as frontline maintenance. In the relapsed platinum-sensitive setting, olaparib, niraparib and rucaparib are effective maintenance options in m patients who are PARPi naive. Both olaparib and rucaparib are effective options in m metastatic castrate-resistant prostate cancer (mCRPC). Evidence also exists for the benefit of PARPi combinations in mCRPC. In metastatic pancreatic cancer, olaparib can be used in gm patients who are responding to platinum chemotherapy. However, there may be a development of PARPi resistance. Understanding the pathophysiology that contributes to such resistance may allow the development of novel therapeutics. Combination therapy appears to have promising results in emerging trials. Seeking avenues for subsidised genetic testing can reduce the total costs of cancer management, leading to improve detection rates.
Identifying breast, ovarian, pancreatic and prostate cancer patients with gm plays a crucial predictive role in selecting those who will benefit significantly from PARPi therapy. The use of PARPi in gm HBOC-related cancers has resulted in significant survival benefits. Beyond 1/2, HRR gene assessment and the consideration of other cancer predisposition syndromes may allow more patients to be eligible for and benefit from targeted therapies.
识别携带生殖系突变(germline mutation,gm)的患者对于促进筛查策略、预防措施以及在其管理中使用靶向治疗至关重要。本综述探讨了与gm相关癌症的最新预测和治疗方法的证据。
数据支持在携带gm的高危HER2阴性乳腺癌患者中使用辅助奥拉帕利。在晚期携带gm的HER2阴性乳腺癌中,聚(ADP-核糖)聚合酶抑制剂(PARPis)他拉唑帕利和奥拉帕利已显示出优于标准化疗的疗效。在卵巢癌中,奥拉帕利、尼拉帕利或卢卡帕利可作为一线维持单药治疗。奥拉帕利和贝伐单抗联合使用也可作为一线维持治疗。在铂敏感复发的情况下,奥拉帕利、尼拉帕利和卢卡帕利是对PARPi初治的携带gm患者有效的维持治疗选择。奥拉帕利和卢卡帕利在携带gm的转移性去势抵抗性前列腺癌(mCRPC)中都是有效的治疗选择。也有证据表明PARPi联合治疗对mCRPC有益。在转移性胰腺癌中,奥拉帕利可用于对铂类化疗有反应的携带gm患者。然而,可能会出现PARPi耐药。了解导致这种耐药的病理生理学可能有助于开发新的治疗方法。联合治疗在新兴试验中似乎有很有前景的结果。寻求补贴基因检测的途径可以降低癌症管理的总成本,从而提高检测率。
识别携带gm的乳腺癌、卵巢癌、胰腺癌和前列腺癌患者在选择能从PARPi治疗中显著获益者方面起着关键预测作用。在携带gm的遗传性乳腺癌卵巢癌综合征(HBOC)相关癌症中使用PARPi已带来显著的生存获益。除了BRCA1/2,HRR基因评估以及考虑其他癌症易感综合征可能会使更多患者有资格接受并从靶向治疗中获益。