Aging-associated changes in the tumour microenvironment determine cancer progression and metastasis
Lead Research Organisation:
University of Oxford
Department Name: Oncology
Abstract
Keywords: Aging, Cancer, Physiology
Age is the greatest risk factor for developing cancer, with majority of cancer cases diagnosed in aged patients.1, 2, 3 Many researchers have argued for years that this association is simply due to increased exposure time to mutagens in older individuals4, 5. With ever increasing recognition of the critical role of the microenvironment in tumourigenesis, a more direct role for ageing-associated processes in cancers is beginning to emerge6. Indeed, researchers have started exploring how aging makes host tissues more or less susceptible to tumour initiation, progression and metastasis7. There is a striking overlap in many aging and cancer processes including DNA damage responses, telomere attrition, replicative senescence, endocrine and immune modulations, and angiogenesis 7-12 . These similarities merit a systematic, in-depth understanding of the role of ageing processes in cancers. These processes may be crucial for developing preventive strategies and effective therapies against cancers. Moreover, substantial age-associated differences in incidence and progression are observed between cancer sites that probably reflect different processes and risk factors that are specific to each tissue and tumour type (Fig 1).
Here we propose a highly novel project that moves beyond reductionist approaches and integrates processes at the molecular, cellular and physiological levels to understand the links between aging and cancer.
The main goal will be to address the following research questions using colorectal and prostate cancer models:
How do age-related endocrine changes influence cancer development?
How does immune-system dysfunction contribute to cancer susceptibility?
Does increased inflammation with age contribute to colorectal cancer development?
Can we translate findings from the biology of ageing to fight cancer?
This project will be done in collaboration with our clinical colleagues (e.g. Dr James East) at John Radcliffe Hospital who will provide human samples (e.g colon, prostate). We will also use mouse and cell line models of colon/prostate cancer to study cancer progression and metastasis in an aging microenvironment.
Age is the greatest risk factor for developing cancer, with majority of cancer cases diagnosed in aged patients.1, 2, 3 Many researchers have argued for years that this association is simply due to increased exposure time to mutagens in older individuals4, 5. With ever increasing recognition of the critical role of the microenvironment in tumourigenesis, a more direct role for ageing-associated processes in cancers is beginning to emerge6. Indeed, researchers have started exploring how aging makes host tissues more or less susceptible to tumour initiation, progression and metastasis7. There is a striking overlap in many aging and cancer processes including DNA damage responses, telomere attrition, replicative senescence, endocrine and immune modulations, and angiogenesis 7-12 . These similarities merit a systematic, in-depth understanding of the role of ageing processes in cancers. These processes may be crucial for developing preventive strategies and effective therapies against cancers. Moreover, substantial age-associated differences in incidence and progression are observed between cancer sites that probably reflect different processes and risk factors that are specific to each tissue and tumour type (Fig 1).
Here we propose a highly novel project that moves beyond reductionist approaches and integrates processes at the molecular, cellular and physiological levels to understand the links between aging and cancer.
The main goal will be to address the following research questions using colorectal and prostate cancer models:
How do age-related endocrine changes influence cancer development?
How does immune-system dysfunction contribute to cancer susceptibility?
Does increased inflammation with age contribute to colorectal cancer development?
Can we translate findings from the biology of ageing to fight cancer?
This project will be done in collaboration with our clinical colleagues (e.g. Dr James East) at John Radcliffe Hospital who will provide human samples (e.g colon, prostate). We will also use mouse and cell line models of colon/prostate cancer to study cancer progression and metastasis in an aging microenvironment.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013468/1 | 01/10/2016 | 30/09/2025 | |||
| 1946604 | Studentship | MR/N013468/1 | 01/10/2017 | 31/12/2021 | Sandeep Unwith |