下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Neoadjuvant therapy and translational biomarkers for metastatic risk in early breast cancer.
远处复发仍然是乳腺癌(BC)患者死亡的重要原因。
远处复发仍然是乳腺癌(BC)患者死亡的重要原因。虽然转移曾被认为是晚期事件,但目前的证据表明转移播散在早期即已发生。因此,新辅助治疗(NAT)作为降低转移风险的窗口期受到了广泛关注。虽然NAT传统上由化疗组成,但如今分别向HER2阳性和三阴性(TN)BC患者提供靶向治疗,如人表皮生长因子2(HER2)靶向治疗和免疫检查点抑制剂(ICIs)。随着治疗的演进,越来越需要识别可靠的生物标志物来预测NAT反应并监测NAT后的微小残留病灶。本综述探讨了HER2阳性和TNBC中转移生物标志物与NAT之间的相互作用。循环肿瘤DNA(ctDNA)、循环肿瘤细胞(CTCs)、播散性癌细胞(DCCs)和TIL(肿瘤浸润淋巴细胞)(TILs)为残留病灶、免疫动态和基因组改变提供了纵向洞察。本综述批判性地审视了这些生物标志物在新辅助治疗及更广泛背景下已确立的和新兴的预后、预测和反应适应性作用。新型生物标志物方法的临床采用一直具有挑战性,原因在于其依赖于在本已艰难的治疗过程中进行组织活检。然而,液体活检方法如CTC和ctDNA分析提供了微创监测转移风险的手段。技术进步,如甲基化组测序和基于变异的ctDNA检测,为提高灵敏度和有效性带来了希望。虽然需要进一步试验来确定其临床实用性,但整合这些生物标志物指导的检测可能有助于精确的转移风险评估并改善患者预后。
Distant recurrence remains a significant cause of mortality in patients with breast cancer (BC). While metastasis was once considered a late event, current evidence suggests that metastatic seeding occurs early. There is thus significant interest in neoadjuvant therapy (NAT) as a window of opportunity to decrease metastatic risk. While NAT has classically consisted of chemotherapy, targeted therapies, such as human epidermal growth factor 2 (HER2)-targeted therapies and immune checkpoint inhibitors (ICIs), are now offered to patients with HER2-positive and triple-negative (TN) BC, respectively. As therapies evolve, there is a growing need to identify reliable biomarkers to predict NAT response and monitor microscopic disease post-NAT. This review explores the interplay between metastasis biomarkers and NAT for HER2-positive and TNBC. Circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), disseminated cancer cells (DCCs), and tumour-infiltrating lymphocytes (TILs) provide longitudinal insights into residual disease, immune dynamics, and genomic alterations. This review critically examines the established and emerging prognostic, predictive, and response-adaptive roles of these biomarkers in the neoadjuvant setting and beyond. Clinical adoption of novel biomarker approaches has been challenging due to reliance on tissue biopsy during an already challenging treatment journey. However, liquid biopsy approaches like CTC and ctDNA analyses provide minimally invasive means of monitoring metastatic risk. Technological advancements, such as methylome sequencing and variant-based ctDNA detection, offer promise for improved sensitivity and validity. While further trials are required to establish their clinical utility, integrating these biomarker-informed assays may inform precise metastasis risk assessment and improve patient outcomes.
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