Ring Alexander, Spataro Maria, Wicki Andreas, Aceto Nicola
Department of Biology, Institute for Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Department of Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Front Cell Dev Biol. 2022 Jun 28;10:929893. doi: 10.3389/fcell.2022.929893. eCollection 2022.
Progress in detection and treatment have drastically improved survival for early breast cancer patients. However, distant recurrence causes high mortality and is typically considered incurable. Cancer dissemination occurs circulating tumor cells (CTCs) and up to 75% of breast cancer patients could harbor micrometastatses at time of diagnosis, while metastatic recurrence often occurs years to decades after treatment. During clinical latency, disseminated tumor cells (DTCs) can enter a state of cell cycle arrest or dormancy at distant sites, and are likely shielded from immune detection and treatment. While this is a challenge, it can also be seen as an outstanding opportunity to target dormant DTCs on time, before their transformation into lethal macrometastatic lesions. Here, we review and discuss progress made in our understanding of DTC and dormancy biology in breast cancer. Strides in our mechanistic insights of these features has led to the identification of possible targeting strategies, yet, their integration into clinical trial design is still uncertain. Incorporating minimally invasive liquid biopsies and rationally designed adjuvant therapies, targeting both proliferating and dormant tumor cells, may help to address current challenges and improve precision cancer care.
检测和治疗方面的进展已显著提高了早期乳腺癌患者的生存率。然而，远处复发导致高死亡率，通常被认为无法治愈。癌症播散通过循环肿瘤细胞（CTC）发生，高达75%的乳腺癌患者在诊断时可能已存在微转移，而转移复发往往在治疗后数年至数十年才出现。在临床潜伏期，播散的肿瘤细胞（DTC）可在远处部位进入细胞周期停滞或休眠状态，并可能逃避免疫检测和治疗。虽然这是一个挑战，但也可被视为一个绝佳机会，即在休眠的DTC转化为致命的大转移灶之前及时对其进行靶向治疗。在此，我们回顾并讨论在乳腺癌DTC和休眠生物学认识方面取得的进展。对这些特征的机制性深入了解已促使确定了可能的靶向策略，然而，将其纳入临床试验设计仍不确定。结合微创液体活检和合理设计的辅助治疗，同时靶向增殖和休眠的肿瘤细胞，可能有助于应对当前挑战并改善精准癌症治疗。
