Overview
Mechanochemical dynamic therapy (MDT) is a new ultrasound cancer treatment approach to advancing radical cancer treatment. Utilizing non-destructive ultrasound and innovative mechano-sensitive sensitizers, MDT stimulates the production of reactive oxygen species (ROS), effectively harnessing the combined strengths of photodynamic therapy (PDT) and sonodynamic therapy (SDT). Distinct from its predecessors, MDT addresses the challenges of deep tissue penetration and minimizes the risks associated with cavitation, issues prevalent in traditional SDT and PDT approaches.
Offering a more precise and less invasive treatment method, MDT holds the potential to enhance efficacy and reduce side effects for cancer patients. This year's MDT workshop will explore how this pioneering therapy could transform prostate cancer treatment, inviting participants to discuss and discover the potential breakthroughs MDT offers in this field.
A networking lunch will follow.
Register here: https://forms.illinois.edu/sec/1811058488
Agenda
Introduction | 10:00 a.m.
Mechanochemical Dynamic Therapy
Yun-Sheng Chen, PhD., University of Illinois Urbana-Champaign
Keynote Speaker | 10:15 a.m.
- Developing New Therapeutic Strategies for Cancer
Tanya Stoyanova, PhD, University of California, Los Angeles
Working Group Presentations | 11:00 a.m.
- Mechanochemical Dynamic Cancer Therapy Using FUS-triggered Mechanophores
Jian Wang, PhD., University of Illinois Urbana-Champaign - How Do Ultrasound-Induced Reactive Oxygen Species Affect Autophagy and Apoptosis In Drug-Resistant Prostate Cancer Cells?
Xingxing Wang, PhD., University of Illinois Urbana-Champaign
Networking Lunch | 12:00 p.m.
Keynote Speaker
Tanya Stoyanova, PhD
Associate Professor, Molecular and Medical Pharmacology and Urology
University of California, Los Angeles
Dr. Stoyanova received her Ph.D. in Biochemistry and Molecular Genetics at the University of Illinois, Chicago in Dr. Pardip Raychaudhuri’s laboratory in July 2009, followed by a postdoctoral fellowship in prostate cancer biology at the University of California, Los Angeles in the laboratory of Dr. Owen Witte. In November 2015, Dr. Stoyanova joined the Department of Radiology and the Canary Center for Cancer Early Detection at Stanford University as an Assistant Professor.
In 2023, Dr. Stoyanova joined the Department of Molecular and Medical Pharmacology and Department of Urology at the University of California, Los Angeles. Stoyanova laboratory’s research focuses on understanding fundamental molecular mechanisms underlying the development of epithelial cancers and their utility as biomarkers and therapeutic targets. The ultimate goals of Stoyanova laboratory are to improve cancer early detection and aid the development of better therapeutic strategies for metastatic cancer. The impact of her research has been recognized by multiple awards including the Prostate Cancer Foundation Young Investigator Award, National Institutes of Health Pathway to Independence Award, Stanford McCormick and Gabilan Faculty Award, Society for Basic Urologic Research Young Investigator Award, National Institutes of Health/National Cancer Institute R37 MERIT Award and multiple awards from the Department of Defense. Dr. Stoyanova serves as a Principal Investigator on multiple National Cancer Institute R01 grants, Department of Defense awards and World Wide Cancer Research Grants.
Plenary Speaker Abstracts
Mechanochemical Dynamic Cancer Therapy Using FUS-triggered Mechanophores
Photodynamic therapy (PDT) and sonodynamic therapy (SDT), using non-ionizing light and ultrasound respectively to generate reactive oxygen species, offer promising localized treatments for cancers. However, the effectiveness of PDT is hampered by inadequate tissue penetration and SDT largely relies on pyrolysis and sonoluminescence, which may cause tissue injury and imprecise targeting. To address these issues, we developed injectable, nanoscale mechanophore particles with enhanced ultrasound sensitivity by leveraging a core-shell structure comprising silica nanoparticles (NPs) whose interface is linked to polymer brushes by an azo mechanophore moiety. The mechanophore is a force-sensitive molecular unit that possesses mechanically labile bonds. When incorporated into mechanically stressed polymers, mechanophores can be selectively activated over polymer backbones, resulting in desirable physical or chemical transformations. Upon focused ultrasound (FUS) treatment, azo mechanophores will be activated and generate two radicals and these radicals will be converted into reactive oxygen species (ROS) in the presence of oxygen. The ROS generated from this novel injectable NP show promising results in both an in vitro 4T1 cell model and an in vivo mouse model of orthotopic breast cancers. This research offers an alternative therapy technique, integrating force-responsive azo mechanophores and FUS under biocompatible conditions.
How Do Ultrasound-Induced Reactive Oxygen Species Affect Autophagy and Apoptosis in Drug-Resistant Prostate Cancer Cells?
Ultrasound-induced reactive oxygen species (ROS) represent an emerging alternative for treating prostate cancers that do not respond to standard chemotherapeutic treatments. The role of ROS in influencing cellular autophagy and apoptosis is well-established; however, their specific effects on prostate cancer cells that resist drug treatment, particularly those resistant to doxorubicin (DOX), are not fully defined. This study investigates the intricate interplay between ultrasound-induced ROS, cellular autophagy, and apoptosis signaling pathways in prostate cancer cells, which are resistant to DOX, an anticancer drug known for the high incidence of drug resistance. We reveal how ROS modulates these cellular processes and specify the conditions under which ultrasound-induced ROS initiates apoptosis in both two-dimensional and three-dimensional cell culture models. The finding provides mechanistic insights into the efficacy of this approach against DOX-resistant prostate cancer at the mRNA and protein levels. In conclusion, our study explores the effect of ROS on DOX-resistant prostate cancer cells. The finding represents a significant step toward developing more effective ultrasound ROS prostate cancer treatments for patients who exhibit resistance to conventional chemotherapy, with potential implications for broader applications in oncology.
