Simon N. Powell
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View article: Changes in child maltreatment occurrence during the COVID-19 pandemic: A systematic review
Changes in child maltreatment occurrence during the COVID-19 pandemic: A systematic review Open
The evidence informing changes in CM from before to during the COVID-19 pandemic is mixed and very uncertain for most outcomes, underpinned by gaps in the CM data collection systems during the pandemic period. Efforts to strengthen CM data…
View article: Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting
Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting Open
Apurinic/apyrimidinic endonucleases - APE1 and APE2 are central to genome maintenance and the cellular DNA damage response, with expanding relevance in cancer biology. APE1 is the primary endonuclease in base excision repair and functions …
View article: The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer
The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer Open
Single-stranded DNA (ssDNA) gaps are a hallmark of BRCA-deficient cells, yet the mechanisms that safeguard these lesions remain unclear. Through a genome-wide CRISPR screen, we identified the RAD9A-HUS1-RAD1 (9-1-1) complex as essential fo…
View article: Adjuvant Radiation and Endocrine Therapy in Early-Stage Breast Cancer With Low Genomic Risk
Adjuvant Radiation and Endocrine Therapy in Early-Stage Breast Cancer With Low Genomic Risk Open
Importance De-escalation of adjuvant therapy is feasible for select older patients with early-stage breast cancer. It is not known whether we can expand de-escalation options for younger patients by incorporating genomic biomarkers, such a…
View article: Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis
Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis Open
Importance Leptomeningeal metastasis (LM) is associated with limited survival and few treatment options. Photon involved-field radiotherapy (IFRT) is the most common radiotherapy treatment for patients with LM from solid tumors. Objective …
View article: Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes
Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes Open
Invasive breast carcinomas associated with microglandular adenosis (IBC-MGA) represent a rare and poorly characterized form of triple-negative breast cancer (TNBC). We analyzed clinical, pathological, and germline genetic data from 38 pati…
View article: AlphaMissense for Identifying Pathogenic Missense Mutations in DNA Damage Repair Genes in Cancer
AlphaMissense for Identifying Pathogenic Missense Mutations in DNA Damage Repair Genes in Cancer Open
PURPOSE AlphaMissense is a new artificial intelligence–based approach to predicting the pathogenicity of missense variants. However, whether its predictions can be directly applied to clinical decision making remains unclear. This study ai…
View article: Radiosensitizing the SUMO stress response intensifies single-dose radiotherapy tumor cure
Radiosensitizing the SUMO stress response intensifies single-dose radiotherapy tumor cure Open
Single-dose radiotherapy (SDRT) is a highly curative modality that may transform radiotherapy practice. Unfortunately, only ~50% of oligometastatic lesions are SDRT treatable due to adjacent radiosensitive normal organs at risk. Here, we a…
View article: APOBEC3 mutagenesis drives therapy resistance in breast cancer
APOBEC3 mutagenesis drives therapy resistance in breast cancer Open
Acquired genetic alterations drive resistance to endocrine and targeted therapies in metastatic breast cancer; however, the underlying processes engendering these alterations are largely uncharacterized. To identify the underlying mutation…
View article: RNA transcripts serve as a template for double-strand break repair in human cells
RNA transcripts serve as a template for double-strand break repair in human cells Open
Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, growing evidence suggests that RNA:DNA hybrids and nearby transcripts can influence …
View article: The cold immunological landscape of ATM-deficient cancers
The cold immunological landscape of ATM-deficient cancers Open
Background Mutations in genes encoding DNA repair factors, which facilitate mismatch repair, homologous recombination, or DNA polymerase functions, are known to enhance tumor immunogenicity. Ataxia telangiectasia mutated ( ATM ) is a centr…
View article: Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low‐Frequency Ultrasound
Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low‐Frequency Ultrasound Open
The presence of senescent cells causes age‐related pathologies since their removal by genetic or pharmacological means, as well as possibly by exercise, improves outcomes in animal models. An alternative to depleting such cells would be to…
View article: RNA Transcripts Serve as a Template for Double-Strand Break Repair in Human Cells
RNA Transcripts Serve as a Template for Double-Strand Break Repair in Human Cells Open
Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, emerging evidence suggests that RNA:DNA hybrids and transcripts near damaged sites c…
View article: Ultrasound‐mediated mechanical forces activate selective tumor cell apoptosis
Ultrasound‐mediated mechanical forces activate selective tumor cell apoptosis Open
Recent studies show that tumor cells undergo apoptosis after mechanical stretching, which promotes normal cell growth. Since ultrasound can produce similar sub‐cellular mechanical stresses on the nanoscale, here we test the effect of ultra…
View article: Supplementary Figures 1 from Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy
Supplementary Figures 1 from Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy Open
Supplementary Figures
View article: Data from Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy
Data from Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy Open
Purpose:The importance of the DNA damage response in mediating effects of radiotherapy (RT) has galvanized efforts to target this pathway with radiosensitizers. Yet early clinical trials of this approach have failed to yield a benefit in u…
View article: Data from Advancing Global Health Equity in Oncology Clinical Trial Access
Data from Advancing Global Health Equity in Oncology Clinical Trial Access Open
Summary:Despite exponentially increased industry investment in oncology research and development with more than $80 billion spent annually, patient enrollment in clinical trials remains below 5% globally. Our multistakeholder international…
View article: Supplementary Figure 2 from Advancing Global Health Equity in Oncology Clinical Trial Access
Supplementary Figure 2 from Advancing Global Health Equity in Oncology Clinical Trial Access Open
Supplementary Figure 2: Number of cancer cases and deaths across geography in 2020, Millions
View article: Supplementary Table 1 from Advancing Global Health Equity in Oncology Clinical Trial Access
Supplementary Table 1 from Advancing Global Health Equity in Oncology Clinical Trial Access Open
Supplementary Table 1: Authors and affiliations
View article: Supplementary Figure 1 from Advancing Global Health Equity in Oncology Clinical Trial Access
Supplementary Figure 1 from Advancing Global Health Equity in Oncology Clinical Trial Access Open
Supplementary Figure 1: Number of cancer cases and deaths across indications in 2020, Millions
View article: Advancing Global Health Equity in Oncology Clinical Trial Access
Advancing Global Health Equity in Oncology Clinical Trial Access Open
Summary: Despite exponentially increased industry investment in oncology research and development with more than $80 billion spent annually, patient enrollment in clinical trials remains below 5% globally. Our multistakeholder internationa…
View article: ASMase is Essential for the Immune Response to Partial-Tumor Radiation Exposure
ASMase is Essential for the Immune Response to Partial-Tumor Radiation Exposure Open
Background/Aims: Tumor response to radiation is thought to depend on the direct killing of tumor cells. Our laboratory has called this into question. Firstly, we showed that the biology of the host, specifically the endothelial expression …