Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, Belgium.
Department of Oncology, Antwerp University Hospital (UZA), Edegem, Belgium.
Anticancer Res. 2022 Jan;42(1):373-379. doi: 10.21873/anticanres.15495.
Soft tissue myoepithelial carcinomas (STMC) are a rare, malignant subgroup of myoepithelial tumors that arise typically in glandular or ductal tissues, but also in the bone and soft and cutaneous tissues. Due to its rarity, there is no consensus regarding the treatment of STMC, including chemotherapy or other systemic agents for metastatic STMC.
A chemotherapy- and regorafenib-refractory STMC, harboring an AGK-BRAF fusion, was successfully treated using MEK-inhibition with cobimetinib in monotherapy. MEK-inhibition with cobimetinib effectively silenced paradoxical MAP kinase/ERK-signaling pathway activation after regorafenib monotherapy, and resulted in a significant and durable clinical response.
This effect of MEK-inhibition in STMC harboring an AGK-BRAF fusion has not been previously reported and contributes to the existing, yet limited, knowledge on the treatment of BRAF fusion-driven tumors. Also, our case highlights the importance of next generation sequencing in driving further rational therapeutic choices to provide disease control and palliation.
软组织肌上皮癌（STMC）是一种罕见的、恶性的肌上皮肿瘤亚组，通常发生在腺体或导管组织中，但也发生在骨、软组织和皮肤组织中。由于其罕见性，对于 STMC 的治疗，包括化疗或其他转移性 STMC 的全身药物治疗，尚无共识。
一例化疗和regorafenib 耐药的 STMC，携带 AGK-BRAF 融合，使用单药 cobimetinib 的 MEK 抑制成功治疗。在 regorafenib 单药治疗后，cobimetinib 的 MEK 抑制有效地沉默了矛盾的 MAP 激酶/ERK 信号通路的激活，并导致了显著和持久的临床反应。
AGK-BRAF 融合的 STMC 中 MEK 抑制的这种作用以前没有报道过，有助于增加对 BRAF 融合驱动肿瘤治疗的现有但有限的认识。此外，我们的病例强调了下一代测序在推动进一步合理治疗选择以提供疾病控制和缓解方面的重要性。
