Publications

Publications

Small Molecule Inhibitors of ERCC1-XPF Protein-Protein Interaction Synergize Alkylating Agents in Cancer Cells

By:
Contributors: Jack Tuszynski Research Group
Mol Pharmacol. 2013 Jul;84(1):12-24. doi: 10.1124/mol.112.082347. Epub 2013 Apr 11.

Abstract

The benefit of cancer chemotherapy based on alkylating agents is limited because of the action of DNA repair enzymes, which mitigate the damage induced by these agents. The interaction between the proteins ERCC1 and XPF involves two major components of the nucleotide excision repair pathway. Here, novel inhibitors of this interaction were identified by virtual screening based on available structures with use of the National Cancer Institute diversity set and a panel of DrugBank small molecules. Subsequently, experimental validation of the in silico screening was undertaken. Top hits were evaluated on A549 and HCT116 cancer cells. In particular, the compound labeled NSC 130813 [4-[(6-chloro-2-methoxy-9-acridinyl)amino]-2-[(4-methyl-1-piperazinyl)methyl]] was shown to act synergistically with cisplatin and mitomycin C; to increase UVC-mediated cytotoxicity; to modify DNA repair as indicated by the staining of phosphorylated H2AX; and to disrupt interaction between ERCC1 and XPF in cells. In addition, using the Biacore technique, we showed that this compound interacts with the domain of XPF responsible for interaction with ERCC1. This study shows that small molecules targeting the protein-protein interaction of ERCC1 and XPF can be developed to enhance the effects of alkylating agents on cancer cells.

 

PubMed

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14th Annual APCaRI Fall Symposium 2022

We’re meeting in person at the Banff Park Lodge (location and directions). This year the symposium features three invited speakers:
Agenda_APCaRI Fall Symposium 2022

Dr. Chris Wallis, MD, PhD
Assistant Professor, University of Toronto and Urologic Oncologist, Mount Sinai Hospital and University Health Network

KEYNOTE on FRIDAY, NOV 18, 3-3:50 pm: “But what if….? Treatment regret in localized prostate cancer”

Christopher Wallis obtained his Doctor of Medicine from the University of British Columbia and his Doctor of Philosophy in Clinical Epidemiology & Health Care Research from the Institute of Health Policy, Management & Evaluation at the University of Toronto. He completed his clinical residency in Urology at the University of Toronto affiliated hospitals and his Society of Urologic Oncology accredited fellowship training at Vanderbilt University Medical Center. To date, he has more than 225 publications in peer-reviewed journals. His research focuses on leveraging epidemiologic techniques to understand the interaction between processes of care and patient outcomes, with a particular focus on patients with cancer and those undergoing surgery.

Dr. Paul Boutros, PhD
Professor, Human Genetics, Department of Urology, University of California, Los Angeles

KEYNOTE on SATURDAY, NOV 19, 9:10-10 am: “The evolution of lethal prostate cancer”

My primary research focus is developing large clinically-coherent cancer cohorts, linked to high-dimensional molecular or imaging data. We develop statistical and machine-learning algorithms to identify novel features and create biomarkers that predict actionable clinical phenotypes. This leads to deep long-term collaborations with clinicians and clinician-scientists, working regularly on clinical trial cohorts to ensure our work has a potential patient impact. I am passionate about ensuring that the data and software resources we create reach wide community usage, and this has led to the second major focus of my research.

Mr. Vijay Pandurangan, Prof. MSc.
Adjunct Professor at Stanford School of Medicine.

KEYNOTE on SATURDAY, NOV 19, 1:30-2:20 pm: “How better software engineering improves scientific and medical research.”

Vijay received his Bachelor’s in Computer Engineering from George Washington and his MSc in Electrical and Computer Engineering from Carnegie Mellon. Following his MSc, Vijay joined Google as one of the company’s earliest software engineers in 2002. He later founded a venture-backed company called Mitro, which focused on building an easy way for teams to save and share passwords, which was acquired by Twitter – where Vijay led the New York engineering team. Following his time at Google and Twitter, Vijay joined Benchmark as an Entrepreneur in Residence. Throughout his 20 years of experience in building software, Vijay has been an avid investor in early-stage startups. His portfolio spans 90+ companies, primarily in the B2B and biotech space, including Wish, Pilot, FabricNano, BigHat Biosciences, and Deel. While working to improve software practices in a cancer immunotherapy startup, Vijay discovered that while the amount of software written by scientists and researchers has inexorably increased, few are aware of best engineering practices, resulting in longer iteration times, more scientific errors and barriers to reproducibility. To bridge this gap, Vijay teaches and advises students and researchers on software engineering techniques to help scientists make their research more rigorous and reproducible, focusing on cloud computing, source control, version management, data storage, and collaboration techniques.

The APCaRI Fall Symposium is always an enriching and fun event! Attendees include clinicians, scientists, clinical research personnel, trainees, benefactors, and representatives of prostate cancer support groups.

THANK YOU TO THE APCARI FALL SYMPOSIUM 2022 SPONSORS AND FUNDING AGENCIES

 

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