Speaker: William B. Ershler, M.D., Institute for Advanced Studies in Aging and Geriatric Medicine, Washington, D. C.
Co-Chairs: Harvey J. Cohen, M.D., Duke University Medical Center Derek Raghavan, M.D., Ph.D., University of Southern California School of Medicine
Recent advances in the scientific understanding of the associations between aging and the development of cancer have facilitated the convergence of research perspectives to identify the molecular alterations in carcinogenesis that are related to the aging process. Common scientific perspectives of biological gerontology and oncology include the following:
Refined technologies and key research achievements in the biology of both aging and cancer in these and other areas hold promise for enhancing the knowledge base on the relationship between aging and the natural history of the major tumors—colon, rectum, prostate, pancreas, lung, bladder, stomach, and breast—for which peak incidence and mortality rates occur in the older population. The aging/cancer relationship is well recognized but not well characterized.
Research on the biology of aging and cancer is clinically important. Stratification of the biological characteristics of tumors with age may reveal which aspects of tumor biology and tumor growth vary in different age groups. The age-related factors that contribute to tumor growth could provide insights that could lead to tailored therapeutic approaches.
The physiologic and other disease conditions of the aged host need to be determined individually to optimize treatment selection. For example, older breast cancer patients are more likely to have estrogen/progesterone-receptor-positive tumors and less abnormal p53 expression than younger patients.
The working group noted that older patients with acute myelogenous leukemia are more likely than younger patients to present with myelodysplasia, have unfavorable cytogenetic profiles, and exhibit inherent drug resistance; they are also less likely to achieve remission. The cytogenetic and molecular genetic subtypes of acute leukemia differ in younger and older persons, and differences in epithelial tumors produce a range of biochemical and molecular changes in older persons, resulting in the vastly different clinical behaviors of these tumors in older and younger patients.
In his introductory remarks, Dr. William B. Ershler posed three questions that were later used to guide discussion in the working group. Dr. Tony Murgo of NCI introduced a fourth, related question in the plenary discussion.
These questions prompted consideration of the seed versus soil hypotheses. According to the seed hypothesis, tumor cells from older individuals are different from those of younger individuals; according to the soil hypothesis, the fundamental features of senescent hosts favor (restrained or increased) tumor growth.
Few data exist to substantiate definitive responses to these questions, but among the theories to explain increased cancer with age are the following:
The NCI-designated cancer centers are in a position to create a critical mass of multidisciplinary professionals with expertise in the biology of aging and of cancer. An interactive network of investigators with appropriate resources and technology could catalyze research efforts to elucidate the relationship between aging and cancer in biology. An infrastructure to increase progress in assessment and intervention in regards to cancer in older persons through detection of premalignant disease, early diagnosis of malignant disease, and optimal treatment is developing (e.g., NIA is supporting studies directed at the aging/cancer interface in the Cancer and Leukemia Group B and Southwest Oncology Group).
A consortium of cancer centers could be developed for successful grant applications to:
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