Personalized Medicine

Oncotarget

Oncotarget published this research paper in Volume 13, entitled, "Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer" by researchers from Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY; Northwell Health Cancer Institute, Lake Success, NY; Feinstein Institutes for Medical Research, Manhasset, NY; Mayo Clinic, Rochester, MN; Northwell Health Department of Pathology, Greenvale, NY.

DOI - https://doi.org/10.18632/oncotarget.28302

Correspondence to - Neal Murphy - nmurphy2@northwell.edu, Annette T. Lee - alee@northwell.edu, and Xin-Hua Zhu - xzhu1@northwell.edu 

Abstract

Introduction: Identifying neoadjuvant chemotherapy (NAC) response in patients with muscle invasive bladder cancer (MIBC) has had limited success based on clinicopathological features and molecular subtyping. Identification of chemotherapy responsive cohorts would facilitate delivery to those most likely to benefit.

Objective: Develop a molecular signature that can identify MIBC NAC responders (R) and non-responders (NR) using a cohort of known NAC response phenotypes, and better understand differences in molecular pathways and subtype classifications between NAC R and NR.

Materials and Methods: Presented are the messenger RNA (mRNA) and microRNA (miRNA) differential expression profiles from initial transurethral resection of bladder tumor (TURBT) specimens of a discovery cohort of MIBC patients consisting of 7 known NAC R and 11 NR, and a validation cohort consisting of 3 R and 5 NR. Pathological response at time of cystectomy after NAC was used to classify initial TURBT specimens as R (pT0) versus NR (≥pT2). RNA and miRNA from FFPE blocks were sequenced using RNAseq and qPCR, respectively.

Results: The discovery cohort had 2309 genes, while the validation cohort had 602 genes and 13 miRNA differentially expressed between R and NR. Gene set enrichment analysis identified mitochondrial gene expression, DNA replication initiation, DNA unwinding in the R discovery cohort and positive regulation of vascular associated smooth muscle cell proliferation in the NR discovery cohort. Canonical correlation (CC) analysis was applied to differentiate R versus NR. 3 CCs (CC13, CC16, and CC17) had an AUC >0.65 in the discovery and validation dataset. Gene ontology enrichment showed CC13 as nucleoside triphosphate metabolic process, CC16 as cell cycle and cellular response to DNA damage, CC17 as DNA packaging complex. All patients were classified using established molecular subtypes: Baylor, UNC, CIT, Lund, MD Anderson, TCGA, and Consensus Class. The MD Anderson p53-like subtype, CIT MC4 subtype and Consensus Class stroma rich subtype had the strongest correlation with a NR phenotype, while no subtype had a strong correlation with the R phenotype.

Conclusions: Our results identify molecular signatures that can be used to differentiate MIBC NAC R versus NR, salient molecular pathway differences, and highlight the utility of molecular subtyping in relation to NAC response.

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Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-predictive-molecular-biomarkers-for-determining-neoadjuvant-chemosensitivity-in-muscle-invasive-bladder-cancer

Keywords - muscle invasive bladder cancer, neoadjuvant chemotherapy, gene expression, molecular subtyping, canonical correlation analysis

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Predictive Biomarkers of Neoadjuvant Chemosensitivity in Muscle Invasive Bladder Cancer 

Technology Networks

Speaking at The Landscape of Cancer Research 2022 online symposium, James Moon from the University of Michigan delivered his talk on next-generation STING agonists for immunotherapy against advanced cancer.

Next-Generation STING Agonists for Immunotherapy Against Advanced Cancer

Speaking at The Landscape of Cancer Research 2022 online symposium, Sofia Lourenco of Cancer Research Horizons delivered her talk on the challenges facing the future of cancer immunotherapies.

Cancer Immunotherapies Landscape: Challenges and Future

Speaking at The Landscape of Cancer Research 2022 online symposium, keynote speaker Grant McFadden of the University of Arizona delivered his talk on recent advances and challenges in oncolytic virotherapy.

Recent Advances and Challenges in Oncolytic Virotherapy: The Myoxma Virus Story

Speaking at ‘Advances in proteomics & Metabolomics’ 2022, Gary Patti from Washington University, presented their talk on precision medicine.

Advancing Metabolomics for Precision Medicine 

Olink proteomics

Inflammation drives a broad spectrum of human diseases.

Professor Emma Guttman, a leading expert in inflammatory skin diseases, discusses why inflammatory protein biomarker analysis is revolutionising her research field. She sees Olink as the agent of change for how we understand and treat inflammatory skin diseases.

Learn more about how protein biomarkers can transform your inflammation research: https://bit.ly/3yOsyUq

Olink - Revolutionising inflammatory skin disease research

Oncotarget published this trending research paper on September 28, 2022 in Volume 13, entitled, "Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival" by researchers from the Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA.

DOI - https://doi.org/10.18632/oncotarget.28277

Correspondence to - Claudia M. Nicolae - cmn14@psu.edu

Abstract

PARP10 is a mono-ADP-ribosyltransferase with multiple cellular functions, including proliferation, apoptosis, metabolism and DNA repair. PARP10 is overexpressed in a significant proportion of tumors, particularly breast and ovarian cancers. Identifying genetic susceptibilities based on PARP10 expression levels is thus potentially relevant for finding new targets for precision oncology. Here, we performed a series of CRISPR genome-wide loss-of-function screens in isogenic control and PARP10-overexpressing or PARP10-knockout cell lines, to identify genetic determinants of PARP10-mediated cellular survival. We found that PARP10-overexpressing cells rely on multiple DNA repair genes for survival, including ATM, the master regulator of the DNA damage checkpoint. Moreover, we show that PARP10 impacts the recruitment of ATM to nascent DNA upon replication stress. Finally, we identify the CDK2-Cyclin E1 complex as essential for proliferation of PARP10-knockout cells. Our work identifies a network of functionally relevant PARP10 synthetic interactions, and reveals a set of factors which can potentially be targeted in personalized cancer therapy.

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Keywords - PARP10, ATM, CRISPR screens, genome stability, cancer cell proliferation

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/OncotargetYouTube
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Trending With Impact: Genome-wide CRISPR Screening Identifies PARP10 Synthetic Interactions

Teach Me in 10

In this episode we are joined by Shane O’Neill, director of scientific affairs at EKF Diagnostics. Shane provides an introduction to the glycated albumin (GA) test for intermediate-term glycemic control in diabetic patients. 

The GA test is now FDA-cleared and available for use in the United States. It was developed by Asahi-Kasei Pharma of Japan (Lucica® brand) and is a standardized and well-evidenced method for determining glycated albumin levels in the serum.

Shane will also describe why glycemic control is important and discuss the value of the test for glycemic monitoring, outlining its clinical utility and how it compares to other markers of glycemic control, such as hemoglobin A1C and fructosamine. 
EKF Diagnostics distributes the test in the United States.

Lucica® Glycated Albumin-L test for diabetes: Comparisons and Clinical Utility With Shane O’Neill

From COVID to chronic infections and cancer, stem cell-derived extracellular vesicles (EVs) have the potential to change the landscape of regenerative medicine and inflammatory conditions treatments. Though still in early-stage research, EVs already appear to hold great promise.

This Teach Me in 10 will cover what EVs are, the therapeutic promise they hold as well as guidance on how to culture and scale.

Personalized Medicine

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