Strategies to Prevent or Remediate Cancer and Treatment-Related Aging.

Up to 85% of adult cancer survivors and 99% of adult survivors of childhood cancer live with an accumulation of chronic conditions, frailty, and/or cognitive impairments resulting from cancer and its treatment. Thus, survivors often show an accelerated development of multiple geriatric syndromes and need therapeutic interventions. To advance progress in this area, the National Cancer Institute convened the second of 2 think tanks under the auspices of the Cancer and Accelerated Aging: Advancing Research for Healthy Survivors initiative.

Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.

Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment.

TGFbeta1 and TGFalpha contrarily affect alveolar survival and tumorigenesis in mouse mammary epithelium.

Growth factors and hormones are responsible for development of the mammary gland and can contribute to mammary carcinogenesis. The transforming growth factors (TGF) alpha and beta1 demonstrate opposing effects on the mammary epithelium. TGFalpha is a mitogen and survival factor for mammary secretory cells and is often upregulated in cancer, while TGFbeta1 may act as a growth suppressor and has been shown to inhibit alveolar development and lactogenesis.

Ultraviolet radiation and cutaneous malignant melanoma.

Recent years have seen a steady rise in the incidence of cutaneous malignant melanoma worldwide. Although it is now appreciated that the key to understanding the process by which melanocytes are transformed into malignant melanoma lies in the interplay between genetic factors and the ultraviolet (UV) spectrum of sunlight, the nature of this relation has remained obscure. Recently, prospects for elucidating the molecular mechanisms underlying such gene-environment interactions have brightened considerably through the development of UV-responsive experimental animal models of melanoma.

Nitric oxide-induced cellular stress and p53 activation in chronic inflammation.

Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G(2)M cell cycle checkpoint.