Publications by authors named "Isla Garraway"

Article Synopsis
  • Therapeutic resistance in cancer, especially in advanced prostate cancer, contributes to high mortality as patients often relapse after initial treatments.
  • Research on circulating tumor cells with increased genomic content (CTC-IGC) from 44 advanced prostate cancer patients reveals a link to poorer survival outcomes and clonal origins, indicating polyploidization.
  • Identification of new RNA and protein markers associated with chemotherapy resistance, such as HOMER1, TNFRSF9, and LRP1, suggests pathways for improving cancer treatment and understanding relapse mechanisms.
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Background: The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3) or serine at 727 (pSTAT3). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway.

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Background: Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors.

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Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of CTC-IGC was significantly associated with poorer progression-free survival.

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Purpose: National guidelines recommend next generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. We sought to describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race/ethnicity, and overall survival in US Veterans.

Patients And Methods: This retrospective cohort study included Non-Hispanic Black (NHB) and Non-Hispanic white (NHW) Veterans with mPCa who obtained NGS through the Veterans Affairs National Precision Oncology Program.

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Background: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities.

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Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival.

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Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity.

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Background: In the United States, Black men are at highest risk for being diagnosed with and dying from prostate cancer. Given this disparity, we examined relevant data to establish clinical prostate-specific antigen (PSA) screening guidelines for Black men in the United States.

Methods: A comprehensive literature search identified 1848 unique publications for screening.

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Importance: Non-Hispanic Black (hereafter, Black) individuals experience worse prostate cancer outcomes due to socioeconomic and racial inequities of access to care. Few studies have empirically evaluated these disparities across different health care systems.

Objective: To describe the racial and ethnic and neighborhood socioeconomic status (nSES) disparities among residents of the same communities who receive prostate cancer care in the US Department of Veterans Affairs (VA) health care system vs other settings.

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Article Synopsis
  • Novel hormonal therapy (NHT) agents improve survival rates in advanced prostate cancer, but there is limited data on their usage across different racial and ethnic groups.
  • This study analyzed the use of NHT among men with de novo advanced prostate cancer using a large Medicare-linked database from 2011 to 2017.
  • Findings revealed that White patients had the highest rate of NHT utilization (27%), compared to Hispanic (25%) and Black (8%) patients, highlighting potential disparities in treatment access and usage.
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Background: Although Black men are more likely than non-Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate-specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self-identified Black than White veterans based on prebiopsy PSA level.

Methods: Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans.

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Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that the HOX/CUT transcription factor ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 targets include the glucocorticoid receptor and the NE splicing factor , among others.

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This letter to the editor responds to comments by Sartor et al regarding recent findings on the clinical relevance of CDK12 pathogenic mutations.

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Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.

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The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

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Context: Prostate cancer (PCa) is a leading cause of death and partially heritable. Genetic risk prediction might be useful for strategies to reduce PCa mortality through early detection and prevention.

Objective: To review evidence for genetic risk prediction for PCa.

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Article Synopsis
  • A study looked at prostate cancer screening among men, focusing on African American (AA) men and non-Hispanic White (NHW) men to see if they were getting screened fairly based on their risk of cancer.
  • They found that fewer AA men reported getting screened compared to NHW men, but factors like income and education made a big difference in those results.
  • The researchers concluded that even though prostate cancer affects AA men more, there are issues like systemic racism and education that impact their access to screening.
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The woefully low proportion of scientists and clinicians underrepresented in medicine (UIM), including members of African-American/Black, Hispanic/Latinx, American Indian/Alaska Native or Native Hawaiian/Pacific Islander communities, is well characterized and documented. Diversity in medicine is not only just, but it improves quality and outcomes. Yet, diversity in academic medicine remains stagnant, despite national recognition and urgent calls to improve diversity, equity, and inclusion across health sciences.

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Article Synopsis
  • The Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project aims to improve understanding of prostate cancer outcomes by creating annotated tissue microarrays from samples globally.
  • Three tissue microarrays were developed for distinct purposes: TMA1 focuses on high-risk localized prostate cancers, TMA2 investigates the effects of androgen deprivation therapy, and TMA3 analyzes molecular marker heterogeneity in metastatic prostate cancer.
  • The project provides a valuable resource for the prostate cancer research community to validate biomarkers and explore critical clinical questions related to disease progression and treatment responses.
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Importance: Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans.

Objective: To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital.

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Importance: Black men have a 2-fold increased risk of dying from prostate cancer compared with White men. However, race-specific differences in response to initial treatment remain unknown.

Objective: To compare overall and treatment-specific outcomes of Black and White men with localized prostate cancer receiving definitive radiotherapy (RT).

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Background: Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients.

Methods: We identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration.

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