MIB Agents OsteoBites and osTEAo

Osteosarcoma Webinar Series: Yanding Zhao, PhD to discuss how Distinct patterns of chromosomal instability fuel osteosarcoma progression and influence patient outcomes.Osteosarcoma (OS) is notable for extreme chromosomal instability (CIN) and molecular heterogeneity, which have hindered therapeutic progress. To address this, the lab performed longitudinal and multi-modal profiling of 91 tumors from 71 pediatric patients, integrating whole-genome and transcriptome sequencing with ATAC-seq and Hi-C in matched cell lines. Their analyses revealed that key driver mutations, including TP53, are fixed early and persist through progression. Over 80% of tumors exhibited complex structural alterations—such as chromothripsis, kataegis, loss of heterozygosity, and ecDNA amplification—with MYC enhancer hijacking linked to chemoresistance. They identified a high-risk evolutionary trajectory marked by homologous recombination deficiency (HRD)-like signatures in the absence of BRCA mutations. These tumors showed focal duplications at fragile sites, early whole-genome doubling, high TP53 mutation burden, and sensitivity to PARP inhibition—highlighting a potential therapeutic vulnerability. Together, these findings define a replication stress–driven model of OS evolution, shaped by early chromosomal remodeling and ecDNA-mediated oncogene activation, with implications for biomarker development and precision treatment strategies.Dr. Yanding Zhao is a postdoctoral researcher at Stanford University in the lab of Dr. Christina Curtis. He earned his PhD in Genetics from Dartmouth College, where he began developing computational tools to understand how genome instability disrupts gene regulation in cancer. At Stanford, his research focuses on pediatric osteosarcoma. By combining genome sequencing, 3D chromatin mapping, and spatial transcriptomics, he studies how tumors evolve, resist treatment, and evade the immune system. Dr. Zhao works closely with clinicians and scientists to help turn these discoveries into potential new therapies. He is honored to be part of the MIB Agents community and looks forward to sharing his work in a way that resonates with patients, families, and advocates.

Osteosarcoma Webinar Series: David Ulmert, MD, PhD, an Associate Professor at UCLA, discusses his OutSmarting Osteosarcoma funded work (Because of Sydney) on high-throughput characterization of pathobiological responses in osteosarcoma tumors treated with LRRC15-targeted radiotherapy to uncover curative co-treatment approaches.Dr. Ulmert will discuss his lab's work investigating how osteosarcoma responds to LRRC15-targeted radiotherapy, with patient translation anticipated this year. Using high-throughput technologies, the team will identify biomarkers, predictive models, and key transcriptional regulators driving the TGFβ–LRRC15 axis. He will review how radiopathobiological changes and immune reprogramming are being mapped to uncover druggable events and inform co-treatment strategies, accelerating near-term impact on patient studies and next-generation therapeutic development.Dr. David Ulmert is an expert in oncology and biotechnology, specializing in cancer biomarkers and targeted therapies. His research focuses on antigens secreted by luminal tissues as novel cancer-specific targets and circulating biomarkers. He developed high-affinity antibodies against androgen receptor-regulated enzymes hK2 and PSA, now in clinical trials across the US, Europe, and Australia—in collaboration with Janssen—for radioimmunotheranostics, CAR-T therapy, and bispecific targeting. His lab also developed DUNP19, an LRRC15-targeting antibody licensed to Lantheus, with a Phase 1 trial in osteosarcoma planned for 2025. Dr. Ulmert leads UCLA’s Preclinical Theranostics Program and conducts population-based studies on cancer biomarkers and risk factors with international collaborators. He is widely recognized for advancing prostate cancer research and translational immunotheranostics.

Osteosarcoma Webinar Series: Joseph Skeate, PhD, an Assistant Professor at the University of Minnesota, discusses his OutSmarting Osteosarcoma funded work (Because of Annaleigh) on next generation dual-CAR gamma delta T cells for the treatment of pediatric osteosarcoma.In this presentation, Dr. Skeate will provide an overview of the next-generation genome engineering strategies deployed for this project and share updates on the development of a gamma-delta chimeric antigen receptor (CAR) T cell therapy for treating osteosarcoma. He will describe how the team is combining non-viral transposon insertion of a CAR transgene with targeted gene modification using an Adenine Base Editor to enhance T cell function in the presence of suppressive factors characteristic of osteosarcoma tumors.Dr Joseph Skeate is an Assistant Professor in the Division of Pediatric Hematology/Oncology at the University of Minnesota. He obtained his PhD in Medical Biology from the University of Southern California Keck School of Medicine. Following his doctoral work, he completed a postdoctoral fellowship at the University of Minnesota under the mentorship of Drs Branden Moriarity and Beau Webber. During this time, he developed a hyperactive transposon system and deployed novel genome engineering approaches using Cas9 systems, creating a powerful toolkit for rapid non-viral engineering and preclinical testing of primary human cells. Leveraging his background and expertise in immunology and genome engineering, his lab now focuses on developing next-generation cellular therapies for rare pediatric disease, including osteosarcoma.

Osteosarcoma Webinar Series: Janeala Morsby, PhD, a postdoctoral associate at St. Jude Children’s Research Hospital, discusses her OutSmarting Osteosarcoma funded work focused on exploring the mechanism of synergy of the dual inhibition of ATM and PARP for the treatment of pediatric osteosarcoma.Janeala Morsby hails from the beautiful island of Jamaica, where she was born and raised in Port Antonio, Portland. Her journey to the United States began when she received a full honors scholarship to attend Claflin University, where she completed her Bachelor of Science in Biochemistry, summa cum laude. She then went on to complete her PhD at the University of Notre Dame under the supervision of Dr. Bradley Smith. At the University of Notre Dame, her work focused on the detection of hypoxia in cancer cell models, in addition to diagnostics and imaging. She is now a postdoctoral associate at St. Jude Children’s Research Hospital (SJCRH) in Dr. Lillian Guenther’s lab. At SJCRH, her work focuses on exploring the mechanism of synergy of the dual inhibition of ATM and PARP for the treatment of pediatric osteosarcoma. She is very passionate about the proposed research project and hopes that the findings of the proposed work will be beneficial to pediatric osteosarcoma patients.

Dr. Kelly Makielski and Dr. Jaime Modiano from the University of Minnesota join us on OsteoBites to discuss comparative extracellular vesicle (EV) biomarkers for osteosarcoma risk and prognosis.They are investigating extracellular vesicle (EV) transcriptomic profiles as minimally invasive biomarkers in canine and pediatric osteosarcoma in two ongoing studies. In the Canine Osteosarcoma Early Detection (COED) study, they are sequencing EV RNA from otherwise healthy dogs in breeds at elevated risk of osteosarcoma to identify gene signatures for the early detection and risk assessment of osteosarcoma. In parallel, they are conducting the KIDsCAN study, where we are sequencing EVs from pediatric osteosarcoma patients to identify prognostic signatures that could ultimately guide treatment intensity, aiming to minimize long-term therapy-associated morbidity without negatively impacting survival. Preliminary results from COED will be shared, along with how their comparative approach is helping to guide the KIDsCAN study.Kelly M. Makielski, DVM, DACVIM (SAIM) is an Assistant Professor of Small Animal Internal Medicine at the University of Minnesota College of Veterinary Medicine and Masonic Cancer Center. Her research focuses on extracellular vesicle (EV) biology and comparative oncology, using naturally occurring cancers in dogs to inform human cancer biology and treatment. She is the recipient of an NIH K01 investigating EV–based biomarkers for osteosarcoma prognosis in pediatric osteosarcoma, to guide personalized therapy and reduce treatment-related morbidity.Dr. Jaime Modiano holds the Alvin and June Perlman Endowed Chair of Animal Oncology and is director of the Animal Cancer Care and Research Program of the College of Veterinary Medicine and the Masonic Cancer Center, University of Minnesota. He completed his training through the Veterinary Medical Scientist Training Program (VMD, PhD) at the University of Pennsylvania, and he followed it with a residency in Clinical Pathology at Colorado State University and a post-doctoral fellowship at the National Jewish Center for Immunology and Respiratory Medicine. Before joining the University of Minnesota, he served on the faculties of Texas A&M University and the University of Colorado Health Sciences Center. Dr. Modiano has also worked in the private sector, as founder of several start-up companies, and as Director of Cancer Immunology and Immunotherapy for the Donald Monk Cancer Research Foundation. Through his research, Dr. Modiano seeks to understand how and why cancer happens and to develop strategies for improving the health and well-being of companion animals and humans alike.

Osteosarcoma Webinar Series: Amy Armstrong, MD, a pediatric oncologist at Siteman Kids, joins us on OsteoBites to discuss an open-label, cohort-sequential dose-escalation and dose-confirmation Phase 1/2 clinical trial to evaluate the safety and efficacy of domatinostat in combination with sirolimus in adolescents and adults with relapsed, refractory sarcoma and osteosarcoma. She will review background, patient selection, treatment plan and study calendar for this clinical trial.Dr. Amy Armstrong is a pediatric oncologist who directs the Solid Tumor Program at Siteman Kids, affiliated with St. Louis Children’s Hospital, as well as co-directs the Adolescent and Young Adult Sarcoma Program in collaboration with Siteman Kids and Siteman Cancer Center. She is an Associate Professor of Pediatrics at Washington University in St. Louis and has research interests in Neurofibromatosis Type 1-related plexiform neurofibromas, renal tumors, and sarcomas found most commonly in the adolescent and young adult population. Dr. Armstrong serves as site Principal Investigator for the Children’s Oncology Group, Neurofibromatosis Clinical Trials Consortium and National Pediatric Cancer Foundation and is invested in conducting and developing clinical trials to serve a diverse range of solid tumors in both the upfront and relapsed setting.

BioOsteosarcoma Webinar Series: Brian Ladle, MD, PhD, Assistant Professor of Oncology and Pediatrics at The Johns Hopkins University School of Medicine, joins us on OsteoBites to discuss deciphering the impact of STING agonists on the tumor microenvironment in osteosarcoma.We have learned that more engagement of the immune system and osteosarcoma results in better outcomes - even when patients are given standard chemotherapy. We have found that drugs that activate the STING pathway in osteosarcoma tumors result in greater immune cell invasion into the tumors. This corresponds with improved outcomes when combined with chemotherapy and other immunotherapies. Dr. Ladle will discuss these findings and what steps we are taking to bring this closer to clinical trials for osteosarcoma patients.Dr. Brian Ladle is a pediatric oncologist, sarcoma specialist, and immunotherapy researcher at Johns Hopkins University. His research centers around the goal of generating potent immune responses against pediatric sarcoma tumors - especially osteosarcoma. Ongoing projects encompass preclinical work using osteosarcoma mouse models and osteosarcoma clinical trials in both dogs and humans. He really believes immunotherapy approaches can be effective against osteosarcoma and will become a key piece to "Make It Better" for osteosarcoma patients.

Osteosarcoma Webinar Series: Karen E. Pollok, PhD, and Pankita H. Pandya, PhD, from the Indiana University School of Medicine, join us on OsteoBites to discuss their work exploring CDK4/6i, particularly in the context of BET inhibition, as a therapeutic option for pediatric OS, regardless of RB status.Hyperactivation of cyclin-dependent kinases 4 and 6 (CDK4/6) has been identified as an actionable molecular signature in pediatric and AYA OS patients at the Indiana University School of Medicine and others. While targeting CDK4/6 has shown promise in significantly reducing tumor progression in many cancers, resistance to CDK4/6 inhibition remains a challenge. To maximize CDK4/6 inhibitor (CDK4/6i) efficacy, a combination therapy will likely be required to mitigate emergence of resistance. Moreover, retinoblastoma proficiency (RB+) has been used as a biomarker to predict response and stratify patients for treatment with CDK4/6 inhibitors in other cancers. This is concerning in the context of OS, since over 70% of OS patients harbor a retinoblastoma deficiency (RB-). Therefore, validation of RB as a biomarker of therapeutic response to CDK4/6 inhibition in OS is needed. The lab's objective in these investigations is to identify rational drug combinations that enhance efficacy of CDK4/6 inhibition, and test prioritized combinations in both RB+ and RB- OS models. Their findings support further exploration of CDK4/6i, particularly in the context of BET inhibition, as a therapeutic option for pediatric OS, regardless of RB status.Dr. Pollok is the Associate Director of Basic Science and Director of the Preclinical Modeling and Therapeutics Shared Resource Facility for the IU Simon Comprehensive Cancer Center (IUSCCC). Dr. Pollok works with cancer research laboratories in the IUSCCC to enhance programmatic science focused on translation to the clinic. In her own lab, she leads a team-oriented research program that brings together basic scientists and clinicians focused on finding cures for aggressive cancers such as sarcomas and brain tumors. Her team utilizes multi-omics data to prioritize the testing of novel combination therapies and has developed over 60 tumor models from pediatric and adolescent patients treated at the Riley Hospital for Children IU Health. In collaboration with Dr. Pankita Pandya and the Pediatric Precision Genomics Program, they employ multi-omics data from these models to focus on testing new molecularly-guided targeted therapies. Their goal is to understand the mechanisms behind therapy-mediated tumor efficacy and emerging resistance.Dr. Pandya is heavily involved in translational team science, where she works in partnership with the Pediatric Precision Genomics Program at the Riley Hospital for Children at IU Health, as well as under the mentorship of Dr. Karen E. Pollok at the Herman B Wells Center. Her research initiatives involve testing novel targeted therapies for improving therapeutic outcomes while minimizing toxicity in pediatric and young adult solid cancers like sarcomas. As a genomics data scientist, she has training in multi-omics data management and mining. Additionally, Dr. Pandya has extensive expertise in in-vivo modeling of aggressive pediatric sarcomas. Such skillsets have enabled Dr. Pandya to identify risk signatures, biomarkers of therapeutic response, and other clinically-relevant therapeutic vulnerabilities in pediatric sarcoma patients for functional validation using molecularly characterized preclinical models that our translational team has developed.

Kelly Faulk, MD, a pediatric oncologist at Children's Hospital Colorado Center for Cancer and Blood Disorders, joins us on OsteoBites to review the open phase 1/1b clinical trial evaluating the combination of losartan and sunitinib in the treatment of pediatric and adult patients with relapsed or refractory osteosarcoma (NCT03900793), including preclinical rationale from canine clinical trials and the trial's design, eligibility, and status.Dr. Kelly Faulk is a pediatric oncologist at Children's Hospital Colorado Center for Cancer and Blood Disorders, where her clinical and research focus is the development of early-phase clinical trials to investigate promising new agents for high-risk pediatric cancers. She is on the Experimental Therapeutics Program (ETP) team and serves as the leader of the High-Risk Leukemia/Lymphoma Program. She has developed and leads several early-phase clinical trials and serves as site principal investigator for numerous others. She completed her medical training at the University of Colorado School of Medicine, did her pediatric residency and pediatric hematology/oncology/bone marrow transplant fellowship at Children's Hospital Colorado, and also completed an additional fellowship in Experimental Therapeutics at Children's Hospital Colorado. She met her wonderful husband Wade in medical school, and they have 3 great kids who keep them busy.

OsteoBites welcomes Yingqi Hua, MD from Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine to discuss his work on molecular subtyping of osteosarcoma, ecDNA, and more.Dr. Hua has been engaged in basic and clinical research of malignant bone tumors for more than 10 years, focusing on the individualized comprehensive treatment of advanced bone tumors, and is committed to transforming research results through clinical research. His research interests include 1. Multi-omics study of osteosarcoma: Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment. 2. Epigenetic study of bone tumors: the function of histone mutation and the function of different histone methylation modification. 3. Drug screen: Screening sensitive drugs by patient derived xenograft(PDX) and explore the mechanism of drug action. 4. Clinical trial of advanced stage sarcomas based on precision medicine.

Matteo Trucco, MD, pediatric oncologist, Director of the Children’s Cancer Innovative Therapy program at the Cleveland Clinic, and chair of the MIB Agents Scientific Advisory Board joins us on OsteoBites to provide a preview of the FACTOR 2025 scientific panels in lay person terms with a brief overview of vocabulary and terms as a helpful resource for patients and families attending our FACTOR 2025 conference.FACTOR 2025 registration is now open! Join us June 26-28th in Salt Lake City. Check out the Scientific Program Register for FACTORThere is a discounted conference room block at the beautiful Grand America Hotel. Book your room. We have a limited number of FACTOR Travel Awards for OsteoWarrriors to attend. OsteoWarriors must be nominated by a healthcare provider. More info on eligibility and guidelines.

Brian Flesner, DVM, MS, DACVIM (Oncology), discusses the recently opened clinical trial studying an Autologous Cancer Vaccine with Checkpoint Inhibitor for the Treatment of Canine Osteosarcoma.The purpose of this study is to evaluate the safety and efficacy of K9-ACV, an autologous killed tumor cell vaccine combined with a novel checkpoint inhibitor (CD200AR-L), compared to standard-of-care chemotherapy for the treatment of canine appendicular osteosarcoma (OSA). K9-ACV has safely been used in over 1,000 dogs, and the vaccine has been shown to display safety in a previous study (without the addition of the checkpoint inhibitor). By evaluating K9-ACV, this trial aims to advance safer, immune-based treatment options for canine cancer that may offer comparable or superior outcomes to chemotherapy.Find more information about this study:https://studypages.com/s/autologous-cancer-vaccine-with-checkpoint-inhibitor-for-treatment-of-canine-osteosarcoma-565406/Adrienne Wright, adrienne@ardentanimalhealth.com, +1 (859) 619-5893

The osteosarcoma community has the power to drive change in childhood cancer research! This important OsteoBites episode features Nancy Goodman, JD, Founder & Executive Director of Kids v Cancer, as she discusses how you can help advocate for the Give Kids a Chance Act—a crucial bill aimed at expanding access to novel combination therapies for kids with cancer.The Give Kids a Chance Act is bipartisan legislation that builds on the RACE for Children Act by requiring pharmaceutical companies to evaluate promising multi-drug combinations in pediatric cancers when those drugs are being tested together in adults. Since many of the most effective cancer treatments involve drug combinations, this bill is essential to improving treatment options for children with osteosarcoma and other pediatric cancers.Be a voice for change! Learn actionable ways to support this bill and ensure kids with cancer have access to more innovative therapies.

Dr. Betsy Young, a physician-scientist from UCSF provides an overview of her funded work: Tumor cGAS-STING repression drives immune evasion in osteosarcoma and is therapeutically targetable via host STING activation. This work was funded by an MIB Agents 2024 OutSmarting Osteosarcoma YI Hope grant Because of Charlotte.Osteosarcoma (OS) has an immunosuppressive macrophage-rich, T-cell-depleted tumor microenvironment (TME). By performing bulk RNA seq of OS cell lines treated with STING agonist, the lab has defined an OS-specific STING activation signature, which demonstrated a significant protective effect on survival in OS patient samples. In immunocompetent OS models, systemic STING agonism shows curative anti-tumor effects, shifts the tumor microenvironment towards a pro-inflammatory phenotype, and induces immunologic memory. Importantly, host STING activation is sufficient to promote this anti-tumor immunity. The lab has demonstrated that STING activation has anti-tumor benefit in animal models and a protective effect in the human disease, nominating this innate immune sensing pathway as an important therapeutic target in OS.As a physician-scientist and a pediatric oncologist, Dr. Young's aim is to advance the field of pediatric oncology in her research career focused on the immunobiology of osteosarcoma. She completed her Pediatric Hematology/Oncology fellowship training at UCSF, receiving strong clinical training in high-risk pediatric solid tumors and early-phase clinical trials. Now, as a faculty member, she is investigating the pathogenesis of osteosarcoma metastasis in the Sweet-Cordero lab at UCSF, with a specific focus on immuno-oncology translational therapeutics.

Matthew Dietz, DO, MSEd joins us on OsteoBites to discuss Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: Consensus Recommendations from the Children’s Oncology Group Bone Tumour Committee.To advance the care and cure for patients with osteosarcoma and Ewing sarcoma it is necessary to safely improve the amount and usability of diagnostic biopsy material obtained. Indeed, it is anticipated that future osteosarcoma and Ewing sarcoma clinical trials will incorporate molecular biomarkers into treatment risk stratification underscoring the need for optimal tissue collection and processing practices.Historically open/incisional biopsies were the predominant biopsy approach; however, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. Including the potential for lower tissue volumes, which can limit components of clinical care - including pathologic assessment, diagnostic accuracy, and molecular evaluations - along with the opportunity for research studies with leftover tissue (following informed consent). Additionally, once biopsy material is obtained the handling of the specimen for histologic and subsequent molecular testing requires careful timing, processing and tissue prioritization to ensure all clinical and research opportunities are preserved for the patient.To help optimize these critical elements in patient care the Children’s Oncology Group convened a multidisciplinary group of clinical and scientific experts to create reference recommendations for harmonizing tissue acquisition and processing algorithms for osteosarcoma and Ewing sarcoma specimens.

Michael Lizardo, MS, PhD, a staff scientist in the Poul Sorensen laboratory at BC Cancer Agency, joins us on OsteoBites to discuss how the pharmacologic inhibition of EIF4A blocks NRF2 synthesis to prevent osteosarcoma metastasis.Dr. Lizardo shares his lab's recent findings in Clinical Cancer Research on how targeting the dysregulated mRNA translation factor eukaryotic initiation factor 4A (EIF4A), via pharmacological inhibitors, prevents the protein synthesis of nuclear factor erythroid 2–related factor 2 (NRF2), which is a cytoprotective protein metastatic OS cells require to successfully colonize the harsh microenvironment of the lung. He also discusses how the EIF4A1 inhibitor, CR-1-31B, and a related clinical-grade compound (Zotatifin) prevent OS cell adaptation to oxidative stress (a major stressor in the lung) in 2D and 3D cell culture models, as well as ex vivo lung organotypic cultures. Moreover, he discusses how drug treatment can inhibit lung metastasis and prolong the survival of animal subjects in pre-clinical mouse models of metastatic OS.

Osteosarcoma Webinar Series: Sowmya Ramesh, PhD joins us on OsteoBites to discuss how multi-modal omics analysis identifies targetable sensory neuron circuitry that promotes sarcoma disease progression.Bone pain is a hallmark of bone cancers, including osteosarcoma (OS), mediated by skeletal-innervating peripheral afferent neurons. However, the roles of tumor-associated sensory neurons in OS beyond pain perception remain poorly understood. To investigate their regulatory functions, a chemical-genetic approach was employed in mice carrying a knock-in allele for TrkA to perturb sensory nerve innervation during OS growth and progression. TrkA inhibition in these transgenic mice significantly reduced sarcoma-associated sensory innervation and vascularization, altered tumor-associated macrophage polarization, decreased tumor growth and metastasis, and extended overall survival.These findings suggest that targeting pathological innervation in OS may serve as an adjunctive therapy to enhance clinical outcomes and survival.Dr. Ramesh is a postdoctoral researcher from the James lab at Johns Hopkins. The lab's research focus lies at the intersection of skeletal pathophysiology and stem cell biology. The lab looks at the interaction of nerves in various musculoskeletal repair including bone repair and regeneration, osteoprogenitor cell characterization, and neoplastic bone. Dr. Ramesh specifically works on understanding how peripheral nerves regulate osteosarcoma disease progression.

Alice Soragni, PhD shares information about PREMOST: an organoid-based functional PREcision Medicine trial in OSTeosarcoma (NCT06064682), a clinical trial that is studying the feasibility of using organoids for predicting drug response and guiding therapy in osteosarcoma.Patient-derived tumor organoids (PDTOs) are lab-grown replicas of tumors that closely resemble the original cancer in both structure and behavior. These models can be rapidly created from small samples obtained during biopsies or surgeries, allowing us to test their responses to different drugs in the lab. This makes them highly valuable for developing personalized treatment strategies, particularly in light of a growing body of evidence showing how PDTOs can in many cases accurately mimic clinical responses. The Soragni Lab has developed a unique platform to grow these organoids efficiently from osteosarcoma surgical samples. They can create these three-dimensional avatars without needing complicated cell sorting or lengthy lab procedures. This means they can start testing drugs and get results within a week of the surgery, a turnaround that is rapid enough to potentially be used in the future to help guide treatment decisions In a pilot study, they found that testing drugs on these organoids provided insights that closely matched the patients' actual clinical outcomes. Osteosarcoma organoids with low viability after neoadjuvant chemotherapy matched patients who experienced higher tumor cell death (necrosis) after treatment and long-term disease status. The lab also investigated responses of PDTOs from advanced, recurrent, and metastatic sarcomas and found that the viability of these organoids in the lab correlated with the time to the next treatment in patients. The data suggests that osteosarcoma organoids could help predict how well some treatments may work. Encouraged by these promising results, the Soragni Lab has initiated a clinical trial to further explore the use of PDTOs to predict osteosarcoma therapy responses. Dr. Soragni will describe the study design for this first-of-its-kind, organoid-based clinical trial in sarcoma.Alice Soragni, PhD, is an Associate Professor in the David Geffen School of Medicine at UCLA, and a member of the Jonsson Comprehensive Cancer Center. She has a Bachelor and Master of Science cum Laude from the University of Bologna, Italy, and a PhD from the ETH of Zuerich, Switzerland. Her laboratory couples basic research into mechanisms of disease to the development of novel therapeutic strategies. Her expertise lies in the development of tumor organoid models to investigate the biology of rare tumors such as osteosarcoma and perform screenings for functional precision medicine applications.

Chris Thomson, DVM, DACVS-SA from Ethos Veterinary Health will discuss the Minimally Invasive Metastasectomy in Canines (MIMIC) clinical trial which will assess the feasibility and tolerability of VATS for lung metastasis and eventually deliver this care as an outpatient procedure. In addition to assessing the therapeutic benefit in canine patients, the study will also pave the way to conduct accelerated studies to identify new drugs to prevent lung metastases in both human and canine osteosarcoma. The hypothesis that a cross-species approach to metastasis biology and drug development will improve outcomes has been widely discussed and adopted but has not delivered on this promise. Better alignment with the OS pediatric and comparative oncology approaches is needed to understand metastasis biology and optimize drug development. Until now, metastasectomy has rarely been performed in veterinary medicine due to the perceived invasiveness of the procedure in older large-breed dogs. Nonetheless, hints of a benefit to canine OS metastasectomy patients exist.Ethos Discovery, a non-profit incubator of scientific innovation, seeks to evolve the existing perspective regarding OS metastasis in dogs and improve the translational approach via their MIMIC (Minimally Invasive Metastasectomy in Canines) trial to create alignment of the dog model with the OS patients of highest need, those with distant metastasis. In this discussion, Dr. Thomson shares their progress and review preliminary findings from the high-level evidence Ethos-MIMIC clinical trial which suggests that there is more hope for patients than initially thought.

Osteosarcoma Webinar Series: Alexander Davies, DVM, PhD joins us on OsteoBites to discuss his work which is focused on dynamic tumor-microenvironment signaling cross-talk, signal integration, and the development of 3D organotypic and tissue models to study these interactions using live-cell microscopy techniques. Results from studies in the Davies Lab demonstrate the utility of a novel dynamic live-cell tissue model, the lungSITE model, to quantitatively measure and understand tumor signaling dynamics and behaviors within the context of the lung metastatic niche. Data obtained from this model provided new insights into how spatial position and temporal response influence signaling dynamics, specifically in osteosarcoma lung metastasis, to create intratumoral signaling heterogeneity and consequent single-cell drug response variation. Dr. Alexander Davies graduated with a Ph.D. in Biochemistry and Molecular Biology and a D.V.M., with an interest in comparative oncology, from the University of California, Davis. He then completed a post-doctoral fellowship in cancer biology at Lawrence Berkeley National Laboratory before joining The Ohio State University as faculty in the Department of Veterinary Biosciences. While at OSU he was a member of the Comprehensive Cancer Center and faculty in the Cancer Biology and Cancer Engineering programs. Currently, Dr. Davies is an Assistant Professor at the Knight Cancer Institute within the Division of Oncological Sciences and Cancer Early Detection Advanced Research Center (CEDAR) where his work focuses on dynamic tumor-microenvironment signaling cross-talk, signal integration, and the development of 3D organotypic and tissue models to study these interactions using live-cell microscopy techniques.