Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach. In this article, we will briefly summarize epidemiology and prognosis of gastroenteropancreatic neuroendocrine carcinomas to emphasize the very low incidence, aggressive nature, and orphan status of this tumor entity. We will also discuss the current pathological classification and its limitations, as well as recent data on their differential biological background compared with small cell lung cancer, and its potential implications for patients care. Then, we will review the standard of care of systemic therapy, basically focused on platinum-based cytotoxic chemotherapy, including some recent randomized trials providing evidence regarding efficacy of irinotecan vs etoposide platinum doublets. Finally, we will present a comprehensive overview of novel therapeutic strategies in current clinical development, including recently reported data on immunotherapy, tumor-agnostic therapies (microsatellite instability, high tumor mutational burden, NTRK and RET gene fusions, BRAF or KRAS inhibitors), and additional treatment strategies targeting other tumor vulnerabilities (ie, Notch pathway, novel targets for radioligand therapy), and provide some insights regarding unmet needs and future perspectives to improve patient's care and prognosis.

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胃肠胰神经内分泌癌的治疗进展：我们正在前进吗？

低分化胃肠胰腺神经内分泌癌是一种侵袭性肿瘤，临床治疗具有挑战性。一小部分早期疾病患者可能实现长期生存，但大多数患者出现快速致命的转移性疾病。目前的护理标准仍然遵循小细胞肺癌（一种更常见的 G3 神经内分泌肿瘤）的治疗模式，尽管新出现的分子和临床数据越来越多地质疑这种方法。在本文中，我们将简要总结胃肠胰腺神经内分泌癌的流行病学和预后，以强调该肿瘤实体的发病率极低、侵袭性和孤儿状态。我们还将讨论当前的病理分类及其局限性，以及与小细胞肺癌相比其不同生物学背景的最新数据及其对患者护理的潜在影响。然后，我们将回顾全身治疗的护理标准，主要集中于铂类细胞毒性化疗，包括最近的一些随机试验，提供有关伊立替康与依托泊苷铂双药疗效的证据。最后，我们将全面概述当前临床开发中的新型治疗策略，包括最近报道的免疫疗法、肿瘤不可知疗法（微卫星不稳定性、高肿瘤突变负荷、NTRK 和 RET 基因融合、BRAF 或 KRAS 抑制剂）以及针对其他肿瘤脆弱性的其他治疗策略（即Notch途径、放射配体治疗的新靶标），