Resilience in older adults with cancer: A scoping literature review.

INTRODUCTION: Resilience, the ability to respond to stressors by maintaining or rapidly returning to normal homeostasis, serves as a new paradigm to improve the care of older adults. However, resilience research in oncology is nascent. We aimed to describe the current research landscape on physical, cognitive, and psychosocial resilience in older cancer patients. MATERIALS AND METHODS: We searched PubMed/MEDLINE from inception to January 28, 2022 for records with the terms "resilient OR resilience OR resiliency." We included studies that focused on persons over age 65 with cancer and assessed physical, cognitive, or psychological resilience. We excluded studies that did not report original data; did not have the full text available; assessed resilience on fewer than three time points; and published in non-English languages. Definitions and measures of resilience were extracted and categorized using qualitative analysis. RESULTS: Of 473 articles screened, we found 29 articles that met criteria for inclusion in our review. There was a high degree of heterogeneity in the definitions and measures of resilience. Resilience was defined as robustness/resistance to decline (n = 11), recovery from trauma/stressor (n = 7), and adaptive and proactive coping behaviors (n = 6). Ten papers did not define resilience. 21 studies utilized longitudinal analysis, five studies used randomized and nonrandomized control trials, and four studies assessed pre-post analysis. Stressors included cancer diagnosis (n = 18), chemotherapy (n = 3), radiation (n = 3), acute illness (n = 3), surgery (n = 2), and hematopoietic cell transplant (n = 1). DISCUSSION: Evidence for predictors and determinants of resilience in older adults with cancer is limited by the absence of standardized definitions and measurements. There is a fundamental need for a more precise definition, measures, and understanding of the physiologic mechanisms underlying the response to the physical, cognitive, and psychosocial stressors of cancer and its treatments.

Strategies to Improve Participation of Older Adults in Cancer Research.

Cancer is a disease associated with aging. As the US population ages, the number of older adults with cancer is projected to dramatically increase. Despite this, older adults remain vastly underrepresented in research that sets the standards for cancer treatments and, consequently, clinicians struggle with how to interpret data from clinical trials and apply them to older adults in practice. A combination of system, clinician, and patient barriers bar opportunities for trial participation for many older patients, and strategies are needed to address these barriers at multiple fronts, five of which are offered here. This review highlights the need to (1) broaden eligibility criteria, (2) measure relevant end points, (3) expand standard trial designs, (4) increase resources (e.g., institutional support, interdisciplinary care, and telehealth), and (5) develop targeted interventions (e.g., behavioral interventions to promote patient enrollment). Implementing these solutions requires a substantial investment in engaging and collaborating with community-based practices, where the majority of older patients with cancer receive their care. Multifaceted strategies are needed to ensure that older patients with cancer, across diverse healthcare settings, receive the highest-quality, evidence-based care.

The Evolving Complexity of Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer: Special Considerations in Older Breast Cancer Patients-Part II: Metastatic Disease.

Breast cancer is a disease of aging, and the incidence of breast cancer is projected to increase dramatically as the global population ages. The majority of breast cancers that occur in older adults are hormone-receptor positive, human epidermal growth factor receptor-2 (HER2)-negative phenotypes, with favorable tumor biology; yet, because of underrepresentation in clinical trials, less evidence is available to guide the complex care for this population. Providing care for older patients with metastatic breast cancer, with coexisting medical conditions, increased risk of treatment toxicity, and frailty, remains a clinical challenge in oncology. In this review, we provide an overview of the current evidence from clinical trials and subanalyses of older adults with hormone receptor-positive, HER2-negative metastatic breast cancer, highlighting data on the safety and efficacy of oral therapies, including endocrine therapy alone or in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. In addition, we note the significant underrepresentation of older and frail adults in these studies. Current and future directions in research for this special population, in order to address significant knowledge gaps, include the need to improve long-term adherence to hormonal and targeted therapy, prospective clinical trials that capture clinical and biological aging endpoints, and the need for a multidisciplinary approach with integration of geriatric and oncology principles.

Regulation of RhoB Gene Expression during Tumorigenesis and Aging Process and Its Potential Applications in These Processes.

RhoB, a member of the Ras homolog gene family and GTPase, regulates intracellular signaling pathways by interfacing with epidermal growth factor receptor (EGFR), Ras, and phosphatidylinositol 3-kinase (PI3K)/Akt to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. Functionally, RhoB, part of the Rho GTPase family, regulates intracellular signaling pathways by interfacing with EGFR, RAS, and PI3K/Akt/mammalian target of rapamycin (mTOR), and MYC pathways to modulate responses in cellular structure and function. Notably, the EGFR, Ras, and PI3K/Akt pathways can lead to downregulation of RhoB, while simultaneously being associated with an increased propensity for tumorigenesis. RHOB expression has a complex regulatory backdrop consisting of multiple histone deacetyltransferase (HDACs 1 and 6) and microRNA (miR-19a, -21, and -223)-mediated mechanisms of modifying expression. The interwoven nature of RhoB's regulatory impact and cellular roles in regulating intracellular vesicle trafficking, cell motion, and the cell cycle lays the foundation for analyzing the link between loss of RhoB and tumorigenesis within the context of age-related decline in RhoB. RhoB appears to play a tissue-specific role in tumorigenesis, as such, uncovering and appreciating the potential for restoration of RHOB expression as a mechanism for cancer prevention or therapeutics serves as a practical application. An in-depth assessment of RhoB will serve as a springboard for investigating and characterizing this key component of numerous intracellular messaging and regulatory pathways that may hold the connection between aging and tumorigenesis.

Analysis of glutathione levels in the brain tissue samples from HIV-1-positive individuals and subject with Alzheimer's disease and its implication in the pathophysiology of the disease process.

HIV-1 positive individuals are at high risk for susceptibility to both pulmonary tuberculosis (TB) and extra-pulmonary TB, including TB meningitis (TBM) which is an extreme form of TB. The goals of this study are to determine the mechanisms responsible for compromised levels of glutathione (GSH) in the brain tissue samples derived from HIV-1-infected individuals and individuals with Alzheimer's disease (AD), investigate the possible underlying mechanisms responsible for GSH deficiency in these pathological conditions, and establish a link between GSH levels and pathophysiology of the disease processes. We demonstrated in the autopsied human brain tissues that the levels of total and reduced forms of GSH were significantly compromised in HIV-1 infected individuals compared to in healthy subjects and individuals with AD. Brain tissue samples derived from HIV-1-positive individuals had substantially higher levels of free radicals than that derived from healthy and AD individuals. Enzymes that are responsible for the de novo synthesis of GSH such as γ-glutamate cysteine-ligase catalytic subunit (GCLC-rate limiting step enzyme) and glutathione synthetase (GSS-enzyme involved in the second step reaction) were significantly decreased in the brain tissue samples derived from HIV-1-positive individuals with low CD4 + T-cells (< 200 cells/mm(3)) compared to healthy and AD individuals. Levels of glutathione reductase (GSR) were also decreased in the brain tissue samples derived from HIV-1 infected individuals. Overall, our findings demonstrate causes for GSH deficiency in the brain tissue from HIV-1 infected individuals explaining the possible reasons for increased susceptibility to the most severe form of extra-pulmonary TB, TBM.