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Abstract：
Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer (mCRC). Histological transformation is an important mechanism underlying the acquired resistance of non-small cell lung cancer and prostate cancer to targeted therapy. However, no report has examined the role of histological transformation in mCRC. Here, we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti-PD-1 combination therapy. The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor. Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process. The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival. This case calls for more attention to histological transformation in mCRC. Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.
摘要：
获得性抗性是限制转移性结直肠癌(mCRC)治疗的临床疗效的主要问题。组织学转变是非小细胞肺癌和前列腺癌对靶向治疗的获得性耐药的重要机制。然而,没有报告研究了组织学转化在mCRC中的作用.这里,我们报告了第一例在抗血管生成和抗PD-1联合治疗期间，原发性结肠腺癌发生组织学转化的大细胞神经内分泌癌。通过观察到转化的大细胞神经内分泌癌病变保留了在原发性肿瘤中发现的原始突变特征，证实了组织学转化。序贯肿瘤活检和肿瘤标志物的动态变化证明了转化过程。组织学转变不仅导致对相同治疗的不一致反应,而且显著缩短了总生存期。这种情况需要更多关注mCRC的组织学转化。疾病进展后的肿瘤再活检和监测肿瘤标志物的动态变化将有助于识别此类病例。
