Precision cancer medicine: Concepts, current practice, and future developments DOI Creative Commons
Anders Edsjö,

Louise Holmquist,

Birgit Geoerger

et al.

Journal of Internal Medicine, Journal Year: 2023, Volume and Issue: 294(4), P. 455 - 481

Published: Aug. 28, 2023

Abstract Precision cancer medicine is a multidisciplinary team effort that requires involvement and commitment of many stakeholders including the society at large. Building on success significant advances in precision therapy for oncological patients over last two decades, future developments will be significantly shaped by improvements scalable molecular diagnostics which increasingly complex multilayered datasets require transformation into clinically useful information guiding patient management fast turnaround times. Adaptive profiling strategies involving tissue‐ liquid‐based testing account immense plasticity during patient's journey also include early detection approaches are already finding their way clinical routine become paramount. A second major driver development smart trials trial concepts which, complemented real‐world evidence, rapidly broaden spectrum therapeutic options. Tight coordination with regulatory agencies health technology assessment bodies crucial this context. Multicentric networks operating nationally internationally key implementing oncology practice support developing improving ecosystem framework needed to turn invocation benefits patients. The review provides an overview diagnostic tools, innovative studies, collaborative efforts realize medicine.

Language: Английский

Biomarkers of aging DOI Open Access

Hainan Bao,

Jiani Cao, Mengting Chen

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

Citations

204
Clonal hematopoiesis is associated with protection from Alzheimer’s disease DOI Creative Commons

Hind Bouzid,

Julia A. Belk, Max Jan

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(7), P. 1662 - 1670

Published: June 15, 2023

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function myeloid cells, we hypothesized that CHIP may also be associated with risk Alzheimer’s disease (AD), in which brain-resident cells thought have major role. To perform association tests between AD dementia, analyzed blood DNA sequencing data from 1,362 individuals 4,368 without AD. Individuals had lower dementia (meta-analysis odds ratio (OR) = 0.64, P 3.8 × 10 −5 ), Mendelian randomization analyses supported causal association. We observed same found were detected microglia-enriched fraction brain seven eight carriers. Single-nucleus chromatin accessibility profiling brain-derived nuclei six carriers revealed comprised large proportion microglial pool samples examined. While additional studies required validate mechanistic findings, these results suggest role attenuating

Language: Английский

Citations

86
Clonal haematopoiesis and dysregulation of the immune system DOI
Roger Belizaire, Waihay J. Wong, Michelle L. Robinette

et al.

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 595 - 610

Published: March 20, 2023

Language: Английский

Citations

71
Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease DOI Creative Commons

Esra D. Gümüşer,

Art Schuermans, So Mi Jemma Cho

et al.

Journal of the American College of Cardiology, Journal Year: 2023, Volume and Issue: 81(20), P. 1996 - 2009

Published: May 1, 2023

Language: Английский

Citations

68
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets DOI Creative Commons
Shaosen Zhang,

Xinyi Xiao,

Yonglin Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

Citations

62
JAK2 V617F allele burden in polycythemia vera: burden of proof DOI Creative Commons
Alison R. Moliterno, Hannah Kaizer, Brandi Reeves

et al.

Blood, Journal Year: 2023, Volume and Issue: 141(16), P. 1934 - 1942

Published: Feb. 6, 2023

Polycythemia vera (PV) is a hematopoietic stem cell neoplasm defined by activating somatic mutations in the JAK2 gene and characterized clinically overproduction of red blood cells, platelets, neutrophils; significant burden disease-specific symptoms; high rates vascular events; evolution to myelofibrosis phase or acute leukemia. The JAK2V617F variant allele frequency (VAF) key determinant outcomes PV, including thrombosis myelofibrotic progression. Here, we critically review dynamic role mutation pathogenesis natural history suitability VAF as diagnostic prognostic biomarker, utility reduction PV treatment.

Language: Английский

Citations

60
Interleukin-6 Receptor Polymorphism Attenuates Clonal Hematopoiesis-Mediated Coronary Artery Disease Risk Among 451 180 Individuals in the UK Biobank DOI Open Access
Caitlyn Vlasschaert, J. Brett Heimlich, Michael J. Rauh

et al.

Circulation, Journal Year: 2023, Volume and Issue: 147(4), P. 358 - 360

Published: Jan. 23, 2023

IL6 Modulates CHIP/CAD Risk in Full UK Biobank Figure.Genetic attenuation of IL6R signaling is protective against CHIP-associated CAD risk the 450 000-person data set when high-confidence CHIP calls are used.A, Associations between clonal hematopoiesis indeterminate potential (CHIP) with increasing numbers next-generation sequencing reads that support variant and age (top) TERT genetic rs7705526 (middle), assessed a logistic regression binary status as outcome.The genotype was coded an additive model.Odds ratios (ORs) represent per-unit SD increase predictor variable.Bottom, Total number individuals putatively identified at each these thresholds.Five supporting optimal balance sensitivity specificity based on associations variant.B, Cumulative incidence coronary artery disease (CAD) by status, defined least 5 reads.C, When reads, associated incident CAD, p.Asp358Ala single nucleotide polymorphism (SNP) this risk.This association observed for non-DNMT3A large allele frequency (≥10%) but not DNMT3A-CHIP.D, relaxed criteria only 3 greatly attenuated, SNP protective.IL6R indicates interleukin-6 receptor.

Language: Английский

Citations

53
Causes and consequences of clonal hematopoiesis DOI Creative Commons
Lachelle D. Weeks, Benjamin L. Ebert

Blood, Journal Year: 2023, Volume and Issue: 142(26), P. 2235 - 2246

Published: Nov. 6, 2023

Abstract Clonal hematopoiesis (CH) is described as the outsized contribution of expanded clones hematopoietic stem and progenitor cells (HSPCs) to blood cell production. The prevalence CH increases dramatically with age. can be caused by somatic mutations in individual genes or gains and/or losses larger chromosomal segments. a premalignant state; detected are initiating for hematologic malignancies, strong predictor development cancers. Moreover, associated nonmalignant disorders increased overall mortality. that drive clonal expansion HSPCs alter function terminally differentiated cells, including release elevated levels inflammatory cytokines. These cytokines may then contribute broad range increase Specific peripheral coordination count parameters powerfully predict malignancies mortality CH. In this review, we summarize current understanding nosology origins. We provide an overview available tools risk stratification discuss management strategies patients presenting hematology clinics.

Language: Английский

Citations

50
Inflammasomes and Atherosclerosis: a Mixed Picture DOI Open Access
Alan R. Tall, Karin Bornfeldt

Circulation Research, Journal Year: 2023, Volume and Issue: 132(11), P. 1505 - 1520

Published: May 25, 2023

The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) and colchicine trials suggest an important role of inflammasomes their major product IL-1β (interleukin 1β) in human atherosclerotic cardiovascular disease. Moreover, studies mouse models indicate a causal atherosclerosis. However, recent have led to more granular view the Studies hyperlipidemic that prominent activation NLRP3 inflammasome requires second hit such as defective cholesterol efflux, DNA repair, clonal hematopoiesis or diabetes. Similarly humans some mutations promoting increase coronary artery disease risk part by activation. Recent mice point wider AIM2 (absent melanoma 2) including forms These developments precision medicine approach which treatments targeting might be best employed clinical settings involving increased

Language: Английский

Citations

45
Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury DOI Creative Commons
Caitlyn Vlasschaert, Cassianne Robinson‐Cohen, Jian-chun Chen

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 810 - 817

Published: March 1, 2024

Abstract Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased several chronic diseases associated with aging. Here we sought to test whether CHIP increases AKI. In three population-based epidemiology cohorts, found that was greater incident AKI, which more pronounced in patients AKI requiring dialysis and individuals somatic mutations genes other than DNMT3A , including TET2 JAK2 . Mendelian randomization analyses supported causal role promoting Non- -CHIP also nonresolving pattern To gain mechanistic insight, evaluated Tet2 Jak2 V617F two mouse models both models, severe renal proinflammatory macrophage infiltration post-AKI fibrosis. summary, work establishes as genetic mechanism conferring impaired function recovery after via an aberrant inflammatory response mediated by macrophages.

Language: Английский

Citations

31