Johnson Anneka L, Tau Steven, Sloop Austin M, Dai Tianyuan, Roberts Alyssa M, Muskus Patricia, Warren Alexa, Kleist Sierra A, Hampsch Riley A, Jorns Julie M, Zhang Rongxiao, Jarvis Lesley A, Miller Todd W
Department of Molecular and Systems Biology, Dartmouth Geisel School of Medicine, Lebanon, NH 03766, USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
Cancers (Basel). 2025 Jun 9;17(12):1921. doi: 10.3390/cancers17121921.
Standard treatment for patients with early-stage estrogen receptor-positive (ER+) breast cancer often includes sequential adjuvant radiation and endocrine therapies. Unfortunately, ~1/3 of patients eventually experience disease recurrence, partly due to residual disease in the form of drug-tolerant persister cancer cells. The anti-cancer efficacy of radiation therapy is partly attributable to the production of oxyradicals that damage biomolecules. We previously showed that endocrine therapy increases mitochondrial content in ER+ breast cancer cells; we postulated that this may also increase oxidative stress.
Herein, we tested the efficacy of concurrent endocrine and radiation therapies, including both conventional (CDR) and ultra-high dose rate (UHDR) radiation.
We found that estrogen deprivation and radiation inhibit cell growth, induce apoptosis, and force cells into an oxidatively stressed state. DNA damage was almost exclusive to cells treated with the combination of endocrine and radiation therapy. Radiation slowed tumor growth in two xenograft models, and combination with estrogen deprivation prolonged the time to regrowth in ZR75-1 tumors.
These findings indicate that simultaneous treatment with endocrine and radiation therapies can be advantageous, warranting further evaluation to identify tumor features predictive of response to individual and combination treatments.
早期雌激素受体阳性（ER+）乳腺癌患者的标准治疗通常包括序贯辅助放疗和内分泌治疗。不幸的是，约三分之一的患者最终会出现疾病复发，部分原因是存在以耐药性存活癌细胞形式的残留疾病。放射治疗的抗癌功效部分归因于产生损伤生物分子的氧自由基。我们之前表明内分泌治疗会增加ER+乳腺癌细胞中的线粒体含量；我们推测这也可能增加氧化应激。
在此，我们测试了同步内分泌和放射治疗的疗效，包括传统（CDR）和超高剂量率（UHDR）放疗。
我们发现雌激素剥夺和放疗会抑制细胞生长、诱导凋亡，并使细胞进入氧化应激状态。DNA损伤几乎仅见于接受内分泌和放射治疗联合的细胞。放疗在两种异种移植模型中减缓了肿瘤生长，与雌激素剥夺联合使用延长了ZR75-1肿瘤的再生长时间。
这些发现表明，同时进行内分泌和放射治疗可能具有优势，值得进一步评估以确定预测对单一治疗和联合治疗反应的肿瘤特征。
