Institute of Molecular Bioimaging and Physiology (IBFM-CNR), 90015 Cefalù (Palermo), Italy.
National Laboratory of South, National Institute for Nuclear Physics (LNS-INFN), 95123 Catania, Italy.
Int J Mol Sci. 2020 Sep 1;21(17):6337. doi: 10.3390/ijms21176337.
Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.
特定的乳腺癌（BC）亚型由于缺乏成功的治疗方案而预后不良。三阴性乳腺癌（TNBC）亚型，雌激素（ER）、孕激素（PR）和人表皮生长因子-2（HER2）受体阴性，由于其侵袭性和缺乏有效治疗方法，对肿瘤学家来说是一个临床挑战。此外，质子治疗（PT）代表了一种针对难以到达的区域或常规放射治疗（RT）抵抗性癌症的有效治疗方法，成为 TNBC 的一种有前途的治疗选择。我们的研究旨在分析 PT 的体内分子反应及其在 MDA-MB-231 TNBC 异种移植模型中的疗效。TNBC 异种移植模型用 2、6 和 9 Gy 的 PT 照射。进行基因表达谱（GEP）分析和免疫组织化学检测（IHC），以突出参与细胞对辐射反应的特定途径和关键分子。GEP 分析深入揭示了 PT 的分子反应，显示出相当大的免疫反应、细胞周期和干细胞过程调节。只有 9 Gy 的剂量改变了信号的平衡，向促死亡信号倾斜，因为质子束可以很容易地进行剂量递增，从而可以靶向肿瘤，同时避免对周围健康组织的损伤。
