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A pan‐tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors

CA: A Cancer Journal for Clinicians Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh et al. Apr 01, 2025 DOI: 10.3322/caac.21870

Abstract Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical trials.

FDA approves CSF1R inhibitor for rare, non-cancerous joint tumours

Nature Reviews Drug Discovery Asher Mullard Apr 01, 2025 DOI: 10.1038/d41573-025-00045-7

Highlighting American Cancer Society‐funded research in <i>CA: A Cancer Journal for Clinicians</i>

CA: A Cancer Journal for Clinicians Don S. Dizon, Christina M. Annunziata Apr 01, 2025 DOI: 10.3322/caac.21876

FDA approves MEK inhibitor for rare neurofibromas

Nature Reviews Drug Discovery Asher Mullard Apr 01, 2025 DOI: 10.1038/d41573-025-00044-8

Underrepresentation of Hispanic women in science, technology, engineering, mathematics, and medicine

CA: A Cancer Journal for Clinicians Jovanka Gencel‐Augusto, Natasha J. Minaya, Daniel E. Johnson et al. Apr 01, 2025 DOI: 10.3322/caac.21875

Abstract Despite ongoing efforts to increase the number of women in science, technology, engineering, and mathematics (STEM) and in medicine, Hispanic women remain severely underrepresented in these fields. This disparity not only hinders scientific innovation and the delivery of culturally competent medical care but also perpetuates a systemic exclusion. Research specifically addressing the challenges faced by Hispanic women, the extent of underrepresentation in these disciplines, and strategies to mitigate these issues is sparce. The authors conducted a systematic analysis of peer‐reviewed articles to address this gap. The findings reveal a stark underrepresentation of Hispanic women across all examined fields, particularly compared with White women. In addition, the underrepresentation persists when compared with Hispanic men, although the disparity is less pronounced. The authors identify ongoing disparities in promotion, compensation, and retention rates for Hispanic women; present data for barriers to entry and retention; and highlight existing programs and strategies aimed at addressing this underrepresentation. Finally, a framework is presented for future studies and actionable initiatives, and the broader implications of these findings for the field of oncology are highlighted.

ASO targets DNA repair protein to combat Huntington disease

Nature Reviews Drug Discovery Katie Kingwell Apr 01, 2025 DOI: 10.1038/d41573-025-00042-w

Induced proximity pushes beyond protein degraders, as first RIPTAC moves into the clinic

Nature Reviews Drug Discovery Asher Mullard Apr 01, 2025 DOI: 10.1038/d41573-025-00037-7

Clinical Outcomes With Normothermic Pulsatile Organ Perfusion in Heart Transplantation: A Report From the OCS Heart Perfusion Registry

Circulation Josef Stehlik, Maryjane A. Farr, Mandeep R. Mehra et al. Apr 01, 2025 DOI: 10.1161/circulationaha.124.071743

BACKGROUND: A preservation system, the Organ Care System (OCS; TransMedics) uses normothermic pulsatile perfusion during organ transport for heart transplantation. This system has demonstrated favorable outcomes in hearts recovered from extended-criteria donors after brain death (DBD) and donors after circulatory death (DCD). METHODS: The OCS Heart Perfusion Registry collects data on US heart transplantations using the OCS, static cold storage (SCS), or thoracoabdominal normothermic regional perfusion (NRP) and donor hearts recovered from DBD or DCD donors. We analyzed donor and recipient characteristics and posttransplantation outcomes in patients transplanted with OCS donor hearts (either DBD or DCD) compared with SCS hearts, and with OCS hearts from DCD donors compared with those recovered with NRP followed by SCS. Propensity score matching was used in survival analyses to adjust for differences among recipient characteristics. RESULTS: Between 2021 and 2023, 3225 consecutive heart transplantations enrolled from 56 centers were analyzed in the Heart Perfusion Registry. The OCS was used in 854 of 3225 heart transplantations (26.4%), among which 340 (39.8%) were DBD and 514 (60.2%) were DCD donors, whereas 2174 DBD donors were recovered with SCS and another 197 DCD donors with NRP techniques. The OCS-DBD group experienced a greater number of organ offer refusals before final acceptance (13 versus 6; Wilcoxon rank sum, P &lt;0.001) and a longer transport distance (667 miles versus 232 miles; Wilcoxon rank sum, P &lt;0.001) compared with SCS-DBD. Survival at 12 months was similar between the 2 groups (89.9% for OCS-DBD versus 90.6% for SCS-DBD; marginal Cox model, P =0.54). Among the OCS-DCD and SCS-DBD groups, survival at 12 months was also similar (91.0% versus 92.5%, respectively; marginal Cox model, P =0.32). The OCS-DCD and NRP-DCD groups demonstrated similar survival (91.0% versus 91.7%, respectively; log rank, P =0.63), although the transport distance was longer in OCS-DCD compared with DCD with NRP followed by SCS (400 miles versus 223 miles; Wilcoxon rank sum, P &lt;0.001). By 2023, 90% of all OCS donor management and recovery was performed with dedicated organ recovery teams. CONCLUSIONS: We demonstrate that real-world implementation of the OCS for DBD donors (using predominantly a dedicated recovery team) is associated with expanded donor criteria, longer transport distance, and excellent posttransplantation outcomes. In OCS-DCD donors, outcomes parallel those of donors recovered with NRP-DCD and compare favorably with DBD donor organs.

Genetics opens new route to degrader discovery

Nature Reviews Drug Discovery Alex Eccleston Apr 01, 2025 DOI: 10.1038/d41573-025-00040-y

Response by Yu and Cheng to Letter Regarding Article, “Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial”

Circulation Miao Yu, Xiang Cheng Apr 01, 2025 DOI: 10.1161/circulationaha.124.073362

Oral STING agonist inhibits tumour growth

Nature Reviews Drug Discovery Sarah Crunkhorn Apr 01, 2025 DOI: 10.1038/d41573-025-00033-x

Correction to: Prenatal Lipopolysaccharides Exposure Induces Transgenerational Inheritance of Hypertension

Circulation Nian Cao, Cong Lan, Caiyu Chen et al. Apr 01, 2025 DOI: 10.1161/cir.0000000000001325

Adrenomedullin triggers insulin resistance

Nature Reviews Drug Discovery Sarah Crunkhorn Apr 01, 2025 DOI: 10.1038/d41573-025-00032-y

2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Circulation Sunil V. Rao, Michelle L. O’Donoghue, Marc Ruel et al. Apr 01, 2025 DOI: 10.1161/cir.0000000000001309

Aim: The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” incorporates new evidence since the “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction” and the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes” and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction.” The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” and the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.” Methods: A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Structure: Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

A platform for personalized ASO therapeutics

Nature Reviews Drug Discovery Sarah Crunkhorn Apr 01, 2025 DOI: 10.1038/d41573-025-00034-w

Paternal Cardiac Lesion Induces Cardiac Adaptation in Offspring

Circulation Benedetta Coppe, María Galardi-Castilla, Andrés Sanz-Morejón et al. Apr 01, 2025 DOI: 10.1161/circulationaha.124.070323

Reversing lysosomal dysfunction to treat PAH

Nature Reviews Drug Discovery Sarah Crunkhorn Apr 01, 2025 DOI: 10.1038/d41573-025-00035-9

Letter by Kakizaki and Räber Regarding Article, “Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial”

Circulation Ryota Kakizaki, Lorenz Räber Apr 01, 2025 DOI: 10.1161/circulationaha.124.072950

Proximal cysteine residues in proteins promote Nε-carboxyalkylation of lysine residues by α-dicarbonyl compounds

Journal of Biological Chemistry Sudipta Panja, Johanna Rankenberg, Cole Michel et al. Apr 01, 2025 DOI: 10.1016/j.jbc.2025.108377

The Future Is Now: Paradigm Shifts in Heart Transplantation in the United States

Circulation Terrence M. Yau, Subodh Verma Apr 01, 2025 DOI: 10.1161/circulationaha.125.073544