权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

AGING AS A SELECTIVE PRESSURE THAT DRIVES TUMOR PROGRESSION

衰老是驱动肿瘤进展的选择性压力

基本信息

批准号：
10245907
负责人：
Ana da silva Gomes
金额：
$ 148.23万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10245907
关键词：
Affect Age Aging Alzheimer&apos s Disease Biological Aging Cancer Patient Cells Clinical Trials Data Diabetes Mellitus Disease Evolution FDA approved FarGo Genotype Healthcare Systems Human Immunotherapy Incidence Infrastructure Knowledge Lead Malignant Neoplasms Maps Metabolic Mutagens Neoplasm Metastasis Older Population Organism Outcome Patients Phenotype Play Population Primary Neoplasm Process Prognosis Risk Risk Factors Role Sampling Serum Therapeutic Therapeutic Intervention Time Tissues age effect age group age related aged anti-cancer anticancer research anticancer treatment cancer cell cancer diagnosis cancer therapy design guided inquiry human old age (65+)malignant phenotype neglect neoplastic cell new therapeutic target novel therapeutic intervention pre-clinical research pressure response single cell technology tumor microenvironment tumor progression virtual

项目摘要

PROJECT SUMMARY Aging is the major risk factor for cancer incidence, with more than 60% of cancer diagnoses occurring in those aged 65 and above. In addition, anecdotal observations indicate that age affects prognosis and outcome. Yet, very little experimental data dissect the connection of aging, cancer progression and sensitivity to anti-cancer therapies. In fact, the vast majority of preclinical research that guide the discovery of novel therapeutic targets and clinical trials that lead to anti-cancer treatments approved by the FDA neglect to account for the age of the average patient. This lack of understanding of how aging plays a role in cancer is especially troubling considering that the number of new cancer cases is on the rise globally, a fact that is tied to the increase in the proportion of the older population in the world. Biologically the aging process affects the function of every cell in an organism suggesting that a cancer developing in an aged host is a different disease than a cancer developing in a young one. Using human serum samples, I recently demonstrated that tumor progression and metastasis formation occur, at least in part, as a manifestation of global metabolic deregulation of the aged host. This supports the idea that the role of aging in cancer goes far beyond increased exposure time to mutagens and puts the aging process at the center stage coordinating the different aspects required for the evolution of malignant phenotypes. Therefore, in order to effectively treat cancer, we must look beyond the current framework which neglects the role of the cancer patient’s age. Here, we propose that the aged host tumor microenvironment exerts distinct Darwinian pressures that combined with the decline of the host anti-cancer defenses define how tumor cells evolve within the primary tumor, progress into metastatic disease and respond to anti-cancer therapies. Employing a combination of cutting-edge bulk and single cell technologies we expect to systematically delineate how aging affects the phenotypes and genotypes of cancer cells as well as to characterize the effects of the aging process on the composition and interactions of the different components of the tumor microenvironment. Finally, we will directly evaluate if old age affects the response to FDA-approved chemotherapeutic regiments and immunotherapies, and evaluate if strategies known to rejuvenate old tissues can affect the response to these therapeutic interventions. Through these studies, we aim to build the knowledge infrastructure required to design therapeutic strategies that account for the reprogramming that occurs with aging.

项目总结