PO.CT01.04 · 临床试验
分子碘可削弱乳腺癌治疗中的化疗耐药性及不良反应
Molecular iodine impairs chemotherapy resistance and adverse effects in breast cancer treatments
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
乳腺癌在女性癌症患者中的发病率和死亡率均居首位。尽管在预防和早期发现方面已做出努力，但转移和化疗耐药仍是治疗失败的重要因素。我们的团队已证明，分子碘（I2）补充剂与常规化疗联合应用可抑制化疗耐药、减轻副作用的严重程度并延长预期寿命。本研究是一项双盲临床试验（NIH NCT03688958），分析口服I2补充剂单独使用以及与不同新辅助治疗（烷化剂、蒽环类和激素治疗；Neo）联合使用，在早期（II期）和晚期（III期）乳腺癌女性中的效果。在早期组中，22例女性在手术前15-30天接受I2（3 mg/天）或安慰剂（有色水）治疗（12例luminal A；9例luminal B；2例三阴性）。晚期组中，16例患者接受I2或安慰剂，并联合Neo治疗（30-90天）（3例luminal A；6例luminal B；7例三阴性）。手术后，所有患者接受I2（3 mg/天）治疗3年。在手术时，I2补充削弱了化疗耐药（70%）。Neo组和Neo+I2组分别表现出10%和40%的病理完全缓解。3年后，3例安慰剂患者（1例luminal B；2例三阴性）出现复发，1例死亡（三阴性）。相比之下，I2治疗组仅1例患者出现复发（luminal B），且无患者死亡。碘治疗减轻了不良反应，且未损害甲状腺功能。转录组分析（DESeq2）显示，I2补充激活了参与分化和细胞黏附的基因，同时减少了参与侵袭和存活的基因。总之，I2补充可增强Neo的抗肿瘤应答，且独立于所使用的药物治疗或分子癌症类型，支持I2是化疗耐药乳腺癌治疗中有效佐剂的观点。致谢：作者感谢Ana Cecilia Santiago和Laura García的技术支持。本研究由PAPIIT-UNAM IN203425和217223资助。
查看英文原文 English abstract
Breast cancer takes the first place in incidence and mortality among female cancer patients. Despite efforts being made in prevention and early detection, metastasis and resistance to chemotherapy are still important factors in treatment failure. Our group has demonstrated that molecular iodine (I 2 ) supplementation with conventional chemotherapy inhibited chemoresistance, reduced the severity of side effects, and increased life expectancy. This study is a double-blinded clinical trial (NIH NCT03688958) that analyzes the oral I 2 supplement, alone and in combination with different neoadjuvant therapies (alkylating agents, anthracycline, and hormonotherapy; Neo), in women with early (stage II) and advanced (stage III) breast cancer. In the Early group, 22 women were treated with I 2 (3 mg/day) or placebo (colored water) for 15-30 days before surgery (12 luminal A; 9 luminal B; 2 triple negative). For the advanced group, 16 patients received I 2 or placebo, along with Neo treatment (30-90 days) (3 luminal A; 6 luminal B; 7 triple negative). After surgery, all patients received I 2 (3 mg/day) for 3 years. At the time of surgery, I 2 supplementation impaired the chemoresistance (70%). Neo and Neo+I 2 groups exhibited pathological complete response of 10% and 40%, respectively. After 3 years, three placebo patients (1 luminal B; 2 triple negative) presented recurrence, and one died (triple negative). In contrast, only one patient in the I 2 treatment group presented with recurrence (luminal B), yet no patients died. Iodine treatments attenuated adverse effects without compromising thyroid function. Transcriptomic analysis (DESeq2) showed that I 2 supplementation activated genes involved in differentiation and cellular adhesion, while diminishing those involved in invasion and survival. In conclusion, I 2 supplementation enhances the antineoplastic response of Neo, independent of the pharmacological treatments used or the molecular cancer type, supporting the notion that I 2 is an effective adjuvant in the treatment of chemoresistant breast cancer. Acknowledgments: The authors are grateful for the technical support of Ana Cecilia Santiago and Laura García. PAPIIT-UNAM IN203425 and 217223 supported this work.
利益披露 Disclosure
J. V. Gil Leyva, None..
B. Estrada-Jimenez, None..
J. Vega-Mera, None..
X. Ramirez-Morales, None..
A. Ruiz-Diego, None..
E. Delgado-Gonzalez, None..
G. Peralta, None..
B. Anguiano, None..
C. Aceves, None.