Adaptations of breast cancer metastasis to the aging lung

患有乳腺癌的老年妇女的治疗选择往往有限，因为合并疾病以及 化疗的耐受性，通常是晚期转移性乳腺癌的唯一治疗选择。 重要器官转移的临床表现是乳腺癌进展的最后阶段， 乳腺癌相关死亡的罪魁祸首。因此，迫切需要更好地理解基本面 使乳腺癌细胞在远端器官中茁壮成长的机制。随着生物体使整个细胞老化 身体失去功能或不正常地发挥功能；副产品和废物分子在循环中积累 在组织内，结缔组织变得更加坚硬，限制了血液流动和氧气，共同领导 对DNA、蛋白质和脂质造成损害。播散性癌细胞与次级器官的相互作用 对于转移的蓬勃发展是必不可少的，并且在很大程度上依赖于特定器官的生物学。尽管如此， 迄今为止的研究在很大程度上忽略了衰老在乳腺癌和乳腺癌转移中的作用， 而且还没有明确的治疗靶点来帮助老年乳腺癌患者的治疗。 因此，迫切需要了解患者的年龄如何影响肿瘤的发生和转移。 目标是为老年妇女这一特别脆弱的群体制定更好的治疗选择。 为了弥合这一知识差距，我们采取了类似的方法来定义 增强年轻宿主的转移能力，以评估是否存在导致乳腺癌的特定年龄特征 转移。我们的初步数据显示，寄主的年龄显著影响使 转移定植和线粒体代谢是提取的乳腺癌细胞的关键特征 尤其是在老宿主身上的转移。在这里，我们将测试提高线粒体适合性是否是必要的 老年患者乳腺癌转移的特点和衰老过程导致的机制 在这部改编版中。这些研究的成功完成将首次揭示年龄的适应- 诱导乳腺癌转移，从而提供了一种毒性比化疗更小的治疗靶点 反过来有可能增加老年妇女能够接受积极治疗的比例，并 提高他们的生活质量。

Treatment options for older women with breast cancer are often limited due to co-morbidities as well as the tolerability of chemotherapies, often the only therapeutic option for advanced stage metastatic breast cancers. The clinical manifestation of metastasis in a vital organ is the final stage of breast cancer progression and the main culprit of breast cancer related mortality. Thus, there is a pressing need to better understand fundamental mechanisms that enable breast cancer cells to thrive in distal organs. As an organism ages cells throughout the body lose their ability to function or do so abnormally; byproducts and waste molecules build up in circulation and within tissues, and connective tissues become stiffer restricting blood flow and oxygen, collectively leading to damage to DNA, proteins, and lipids. The interaction of disseminated cancer cells with the secondary organ is essential for metastases to thrive and largely dependent on the biology of the specific organs. Despite this, research to date has largely neglected the role of aging in breast cancer as well as breast cancer metastasis, and no therapeutic targets have been identified specifically to aid in the treatment of older breast cancer patients. Thus, there is a pressing need to understand how the age of the patient affects tumorigenesis and metastasis with the goal of developing better treatment options for older women, a particularly vulnerable population. Motivated to bridge this gap in knowledge we took a similar approach to what has been used to define traits that empower metastasis in young hosts to evaluate if there are age-specific traits that enable breast cancer metastasis. Our preliminary data showed that the age of the host significantly affects the traits that enable metastatic colonization and revealed mitochondrial metabolism as a key trait in breast cancer cells extracted from metastases specifically in old hosts. Here, we will test if increased mitochondrial fitness is an essential feature for breast cancer metastasis in old hosts and define the mechanism by which the aging process results in this adaptation. Successful completion of these studies will unveil for the first time an adaptation of age- induced breast cancer metastasis, thus offering a therapeutic target with less toxicity than chemotherapies which in turn has the potential to increase the proportion of older women being able to receive active treatment and improve their quality of life.