Exploring Genetic Outcomes as Frailty Biomarkers

Valdiglesias, Vanessa; Sánchez-Flores, María; Marcos-Pérez, Diego; Lorenzo-López, Laura; Maseda, Ana; Millán-Calentí, José Carlos; Pásaro, Eduardo; Laffón, Blanca

doi:10.1093/gerona/gly085

Cited by 30 publications

(24 citation statements)

References 47 publications

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“…Biomarkers could be used to screen for frailty in older cancer patients and to monitor the potential impact of treatment on this patient population. Sarcopenia, inflammatory, genetic, and immunologic markers have been proposed as potential biomarkers, but their effectiveness to define frailty remains unclear [40,41]. Thus, more clinical research needs to be done in the future to validate how biomarkers could be integrated in older patient management.…”

Section: Discussionmentioning

confidence: 99%

Challenges Facing Radiation Oncologists in The Management of Older Cancer Patients: Consensus of The International Geriatric Radiotherapy Group

Popescu

Karlsson²,

Vinh-Hung

et al. 2019

Cancers

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The management of older cancer patients remains difficult because of data paucity. Radiation oncologists need to identify potential issues which could affect treatment of those patients. A workshop was organized in Barcelona among international radiation oncologists with special interest in the management of older cancer patients on April 22, 2018. The following consensus was reached: 1. Older cancer patients often faced unconscious discriminating bias from cancer specialists and institutions because of their chronological age. 2. Advances in radiotherapy techniques have allowed patients with multiple co-morbidities precluding surgery or systemic therapy to achieve potential cure in early disease stages. 3. The lack of biomarkers for frailty remains an impediment to future research. 4. Access to healthcare insurance and daily transportation remains an issue in many countries; 5. Hypofractionation, brachytherapy, or stereotactic techniques may be ideally suited for older cancer patients to minimize transportation issues and to improve tolerance to radiotherapy. 6. Patients with locally advanced disease who are mentally and physically fit should receive combined therapy for potential cure. 7. The role of systemic therapy alone or combined with radiotherapy for frail patients needs to be defined in future clinical trials because of targeted agents or immunotherapy may be less toxic compared to conventional chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Challenges Facing Radiation Oncologists in The Management of Older Cancer Patients: Consensus of The International Geriatric Radiotherapy Group

Popescu

Karlsson²,

Vinh-Hung

et al. 2019

Cancers

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“…Markers of cellular senescence (including markers of DNA damage, telomere length, and cell cycle arrest) and inflammation associated with aging are being explored [ 32 ]. For instance, the capacity of DNA repair decreases with frailty and parameters of increased DNA breakage (such as increased phosphorylated H2AX levels) could be integrated as objective tools for frailty detection [ 45 ]. Another study demonstrated significantly reduced telomere length in frail patients and its association with an increased risk of death [ 46 ].…”

Section: Frailty: Definition and Assessment In MM Patientsmentioning

confidence: 99%

Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Bonello

Boccadoro

Larocca

2020

Cancers

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Multiple myeloma (MM) mostly affects elderly patients, which represent a highly heterogeneous population. Indeed, comorbidities, frailty status and functional reserve may vary considerably among patients with similar chronological age. For this reason, the choice of treatment goals and intensity is particularly challenging in elderly patients, and it requires a multidimensional evaluation of the patients and the disease. In recent years, different tools to detect patient frailty have been developed, and the International Myeloma Working Group frailty score currently represents the gold standard. It identifies intermediate-fit and frail patients requiring gentler treatment approaches compared to fit patients, aiming to preserve quality of life and prevent toxicities. This subset of patients is underrepresented in clinical trials, and studies exploring frailty-adapted approaches are scarce, making the choice of therapy extremely challenging. Treatment options for intermediate-fit and frail patients might include dose-adapted combinations, doublets, and less toxic combinations based on novel agents. This review analyzes the available tools for the assessment of frailty and possible strategies to improve the discriminative power of the scores and expand their use in real-life and clinical trial settings. Moreover, it addresses the main therapeutic challenges in the management of intermediate-fit and frail MM patients at diagnosis and at relapse.

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“…Dysregulation of HIST1H3 histone cluster family (which is particularly susceptible to acetylation) 23 , has been suggested as a driver mechanism of gliomas 24 . In addition, phosphorylation to H2A histone family member X (H2AX) could provide information regarding frailty severity 25 . On the other hand, posttranslational histone modifications do not affect DNA nucleotide sequence but can modify its availability to the transcriptional machinery.…”

Section: Discussionmentioning

confidence: 99%

Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms

Gómez-Verján

Ramírez‐Aldana

Pérez‐Zepeda

et al. 2019

Sci Rep

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Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as FN1, APP, CREBBP, EGFR playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as HIST1H3 cluster and miR200 family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, TNF-α, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and −18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.

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Exploring Genetic Outcomes as Frailty Biomarkers

Cited by 30 publications

References 47 publications

Challenges Facing Radiation Oncologists in The Management of Older Cancer Patients: Consensus of The International Geriatric Radiotherapy Group

Challenges Facing Radiation Oncologists in The Management of Older Cancer Patients: Consensus of The International Geriatric Radiotherapy Group

Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms

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