Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Int J Mol Sci. 2021 Sep 19;22(18):10126. doi: 10.3390/ijms221810126.
Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex entity with multiple factors involved in this pathogenesis. Although the mechanisms of cancer therapy-induced toxicities are multifactorial, damage to the cardiac and pulmonary tissue as well as subsequent fibrosis and organ failure seem to be the underlying events. The available biomarkers and treatment options are not sufficient and efficient to detect cancer therapy-induced early asymptomatic cell fate cardiopulmonary toxicity. Therefore, application of cutting-edge multi-omics technology, such us whole-exome sequencing, DNA methylation, whole-genome sequencing, metabolomics, protein mass spectrometry and single cell transcriptomics, and 10 X spatial genomics, are warranted to identify early and late toxicity, inflammation-induced carcinogenesis response biomarkers, and cancer relapse response biomarkers. In this review, we summarize the current state of knowledge on cancer therapy-induced cardiopulmonary complications and our current understanding of the pathological and molecular consequences of cancer therapy-induced cardiopulmonary fibrosis, inflammation, immune suppression, and tumor recurrence, and possible treatment options for cancer therapy-induced cardiopulmonary toxicity.
癌症治疗的进展提高了癌症无进展生存率，降低了恶性相关死亡率。胸科癌症患者的治疗选择包括手术干预和应用化学疗法联合电离辐射。尽管取得了这些进展，但癌症治疗相关心肺功能障碍（CTRCPD）是癌症治疗最不理想的副作用之一，导致癌症治疗受限。放化疗或免疫疗法通过诱导活性氧、DNA 损伤、炎症、纤维化、细胞免疫失调、心肺衰竭和无癌患者的非恶性相关死亡，促进急性和慢性心肺损伤，这些患者接受了癌症治疗。CTRCPD 是一种复杂的实体，涉及多种发病机制因素。尽管癌症治疗诱导毒性的机制是多因素的，但心脏和肺组织的损伤以及随后的纤维化和器官衰竭似乎是潜在的事件。目前可用的生物标志物和治疗选择不足以有效检测癌症治疗诱导的早期无症状细胞命运心肺毒性。因此，有必要应用前沿的多组学技术，如全外显子组测序、DNA 甲基化、全基因组测序、代谢组学、蛋白质质谱和单细胞转录组学以及 10X 空间基因组学，以识别早期和晚期毒性、炎症诱导的致癌反应生物标志物以及癌症复发反应生物标志物。在这篇综述中，我们总结了癌症治疗诱导的心肺并发症的现有知识状态，以及我们对癌症治疗诱导的心肺纤维化、炎症、免疫抑制和肿瘤复发的病理和分子后果的现有理解，以及癌症治疗诱导的心肺毒性的可能治疗选择。
