Adaptations of breast cancer metastasis to the aging lung

乳腺癌转移对衰老肺部的适应

• 批准号: 10726328
• 负责人: Ana da silva Gomes
• 金额: $ 21.06万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726328
• 关键词: Adolescent; Affect; Age; Aging; Basic Science; Bile Acids; Biogenesis; Biology; Biology of Aging; Blood flow; Breast Cancer Cell; Breast Cancer Patient; Breast cancer metastasis; Cell Extracts; Cells; Chronic Obstructive Pulmonary Disease; Circulation; Clinical; Clinical Trials; Connective Tissue; DNA; Data; Databases; Diagnosis; Disease; Distal; Enrollment; Environment; FDA approved; FGF19 gene; Family; Fibroblast Growth Factor Receptors; Gene Expression Profile; Genetic; Goals; Growth; Home; Hormone secretion; Implant; Knowledge; Lipids; Longevity; Lung; Lung diseases; Malignant neoplasm of lung; Metastatic Neoplasm to the Lung; Metastatic breast cancer; Mitochondria; Mus; Neoplasm Metastasis; Organ; Organism; Outcome; Oxygen; Patients; Process; Production; Prognosis; Proteins; Quality of life; Receptor Activation; Reporting; Research; Role; Signal Transduction; Testing; Therapeutic; Time; Tissues; Toxicity due to chemotherapy; Vulnerable Populations; Woman; Work; active method; age effect; age related; breast cancer progression; cancer cell; cancer diagnosis; cancer therapy; cancer type; cell age; chemotherapy; comorbidity; defined contribution; empowerment; feeding; fitness; human old age (65+); improved; inhibitor; lung colonization; malignant breast neoplasm; mitochondrial fitness; mitochondrial metabolism; mortality; neglect; new therapeutic target; older women; precision oncology; receptor; receptor for advanced glycation endproducts; response; side effect; success; therapeutic target; trait; transcription factor; triple-negative invasive breast carcinoma; tumor; tumorigenesis; wasting; young woman

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.

患有乳腺癌的老年女性的治疗选择往往因合并症以及相关因素而受到限制。 化疗的耐受性，化疗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，也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原理 使乳腺癌细胞在远端器官中茁壮成长的机制。随着有机体整个过程中细胞的老化 身体失去运作能力或运作异常；副产品和废物分子在循环中积累 在组织内，结缔组织变得更僵硬，限制了血流和氧气，共同导致 对 DNA、蛋白质和脂质造成损害。播散性癌细胞与次要器官的相互作用 对于转移的生长至关重要，并且在很大程度上取决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视了衰老在乳腺癌以及乳腺癌转移中的作用， 目前还没有确定专门帮助治疗老年乳腺癌患者的治疗靶点。 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方案。 为了弥合这一知识差距，我们采取了类似的方法来定义特征： 使年轻宿主的转移能够评估是否存在导致乳腺癌的年龄特异性特征 转移。我们的初步数据表明，宿主的年龄显着影响能够实现的特征 转移定植并揭示线粒体代谢是提取的乳腺癌细胞的关键特征 特别是来自旧宿主的转移。在这里，我们将测试增加线粒体健康是否是必要的 老年宿主乳腺癌转移的特征并确定衰老过程的机制 在这次的改编中。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，从而提供比化疗毒性更低的治疗靶点 反过来有可能增加能够接受积极治疗的老年妇女的比例 提高他们的生活质量。