Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

中文翻译：

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多巴胺激动剂抵抗和侵袭性泌乳素瘤的治疗策略：文献综合分析

尽管大多数催乳素瘤可以通过内分泌治疗和/或手术治疗，但这些肿瘤中有很大一部分可能对内分泌治疗有抵抗力和/或复发并明显侵入周围的解剖结构。因此，侵袭性泌乳素瘤的临床、病理和分子定义对于指导经典和新型治疗方式很重要。在这篇综述中，我们旨在定义多巴胺激动剂抗性和侵袭性催乳素瘤的分子内分泌学特征，以设计未来的多模式治疗。除了手术、替莫唑胺化疗和放疗、肽受体放射性核素治疗、雌激素途径调节剂、孕激素拮抗剂或激动剂、mTOR/akt抑制剂、帕瑞肽、吉非替尼/拉帕替尼、依维莫司、和二甲双胍在临床前模型、轶事案例和小案例系列中进行了测试。此外，绒毛膜促性腺激素、促性腺激素释放激素、TGFβ 和 PRDM2 似乎是治疗侵袭性催乳素瘤的可能未来目标。最后，我们通过询问在 2 年内进行的两次后续手术中哪个肿瘤的增殖指数 (Ki67) 从 5-6% 增加到 26%，实现了大规模侵入性生长，并分泌了大量催乳素水平导致血液中的水平达到 1 605 671 ng/dl。