MIB Agents OsteoBites and osTEAo

MIB Agents Osteosarcoma
  • 5.0 (5)
  • Medicine
  • Updated Biweekly

Each week, MIB Agents talks with the leaders and innovators in osteosarcoma surgery, research, treatment and advocacy. Questions are taken during the webinar and are included in each podcast. More information is available at www.mibagents.org

  1. 6d ago

    osTEAo - More Than Physical: The Mental Toll of Cancer

    In this episode of osTEAo, OsteoWarriors share honest and personal reflections on the mental health challenges that can come with diagnosis, treatment, surgery, and survivorship. They talk about the fear, isolation, and loss of normalcy that often come with cancer, especially as young people trying to navigate school, relationships, identity, and everyday life at the same time. From struggling to ask for help to finding comfort in community and people who truly understand, the discussion highlights the importance of support systems, vulnerability, and open conversations around mental health throughout the journey. This episode also welcomes osTEAo's new co-host, Inaaya!

    1h 20m

  2. May 15

    A Phase 1/2, Study to Evaluate LNTH-2403, a LRRC15-targeted radiopharmaceutical, in Patients with Relapsed/Refractory Osteosarcoma

    David Shulman, MD, joins us on OsteoBites to discuss the newly opened phase 1/2 study to evaluate LNTH-2403, a LRRC15-targeted radiopharmaceutical, in patients with relapsed/refractory osteosarcoma. For many years, LRRC15 has been known to be an important target in osteosarcoma. A prior study showed a strong signal of activity of an LRRC15-targeted therapy in osteosarcoma; however, the development of the agent was not pursued. There is now a novel LRRC15-targeting radiopharmaceutical that has entered clinical trials for patients with osteosarcoma, and Dr. Shulman will provide an overview of this newly opened trial. Dr. David Shulman is a Pediatric Oncologist and clinical/translational researcher at Dana-Farber Cancer Institute, where he also serves as an Assistant Professor of Pediatrics at Harvard Medical School. As the Director of the DFCI AYA Sarcoma Program, he focuses his clinical practice on the specialized care of adolescents and young adults (AYA) diagnosed with sarcomas. His research program, which has received support from the NIH and Harvard Catalyst, is dedicated to improving patient outcomes through the investigation of novel therapeutic approaches and the utility of circulating tumor DNA (ctDNA) as a clinical biomarker. He leads a national liquid biopsy study for patients with Ewing sarcoma and osteosarcoma, known as the LEOPARD study.

    46 min

  3. May 8

    Defining tumor-specific vulnerabilities by mapping oncogenic structural variation in osteosarcoma

    Andrew Clugston, PhD, a postdoctoral fellow in the Sweet-Cordero Lab at UCSF joins us on OsteoBites to discuss his OutSmarting Osteosarcoma funded work, in partnership with the RISE Foundation, on defining tumor-specific vulnerabilities by mapping oncogenic structural variation in osteosarcoma. The genomes of osteosarcoma (OS) cancer cells are among the most complex cancer genomes ever observed. Initially formed by hundreds to thousands of incorrectly repaired DNA breaks (structural variants; SVs), OS genomes contain DNA structures that are unique to that patient and tumor cell, combining genes and regulatory features from across the genome in ways that effectively re-wire that cell’s gene expression mechanisms. OS cells are also susceptible to further SVs over time and in response to treatment, potentially allowing OS tumors to evolve rapidly. But these complex and tumor-specific genomic structures may also harbor tumor-specific vulnerabilities. By mapping the many unique DNA structures among patient-derived OS tumor cells, Dr. Clugston has attempted to demonstrate that it is possible both to describe the essential structures within these cells and to search them for novel target genes vulnerable to existing drugs and treatment protocols. Using chromatin conformation capture sequencing (HiC) to observe the shape of the genome and optical genome mapping (OGM) to identify tumor-specific DNA structures, Dr. Clugston has produced tumor-specific maps for multiple patient-derived OS tumor cell lines and has begun development of a search process based on long-read mapping techniques that he hopes will inform future patient-specific treatment protocols. Andrew Clugston grew up in the small town of Lake Luzerne, New York. He received a BS in Biochemistry and an MS in Chemistry at the Rochester Institute of Technology, and he received his PhD in Integrative Systems Biology at the University of Pittsburgh. During his PhD he learned to use and develop bioinformatics tools and techniques to study the role of the genome in kidney as well as eye development, and in the process became fascinated with the importance of 3-dimensional organization in regulating cell behavior. Andrew has since joined the Sweet-Cordero laboratory in the Pediatric Oncology Division at the University of California San Francisco as a Postdoctoral Fellow. There, he applies his knowledge and skillset to study how disruptions in these organizational principles allow osteosarcoma cells to develop and proliferate, and how these changes reveal tumor-specific vulnerabilities that can be exploited for fast and effective treatment options that improve the lives of patients.

    1h 10m

  4. Apr 24

    Targeting Perioperative Myeloid Responses Through NOD/RIPK2 Modulation to Prevent Metastatic Progression in Osteosarcoma

    OsteoBites welcomes Caroline Maloney, MD, PhD, from the Medical College of Wisconsin, who will discuss her research on surgery-accelerated metastasis and developing perioperative therapies. Pulmonary metastasis remains the major cause of death in osteosarcoma. The timing of metastatic relapse defines clinically meaningful subgroups in osteosarcoma with patients who relapse within 6–12 months of surgical removal of their primary tumor having markedly worse survival (10-20%) than those who relapse after completion of therapy (40-50%). While surgical removal of the primary tumor is a fundamental component of the clinical care of solid tumors, surgery induces transient but profound changes in immune and inflammatory responses that can paradoxically accelerate the growth of metastatic disease. Dr. Maloney has demonstrated that surgical removal of the primary tumor accelerates the growth of pre-existing pulmonary metastatic disease and promotes expansion of M2‐like macrophages in the lung microenvironment. Strikingly, short term perioperative treatment with a RIPK2 inhibitor blocks this effect and reprograms macrophages toward an M1-like phenotype, implicating the NOD2–RIPK2 innate immune pathway as a key mediator of post‐surgical immune reprogramming. In contrast, the NOD2 agonist Mifamurtide has shown clinical efficacy when administered as adjuvant therapy to metastatic osteosarcoma patients after primary tumor resection. This data suggests that NOD/RIPK2 signaling may exert context-dependent effects, promoting either pro- or anti-tumor myeloid responses depending on the timing of activation relative to surgery. Understanding how surgical tumor removal alters systemic innate immunity and how RIPK2 signaling orchestrates these responses could identify new strategies to prevent early pulmonary relapse after surgery.

    1h 1m

  5. Apr 16

    osTEAo: The Sound of Strength

    In this episode of osTEAo, the group explores how music is a powerful tool for coping with cancer - helping patients process emotions, find comfort during treatment, and stay connected to themselves and others. From meaningful song interpretations to personal stories of healing, the conversation highlights the impact of music. The episode also features a heartfelt farewell to co-host Mia as she reflects on her osTEAo journey and the community behind the podcast.

    1h 3m

  6. Apr 10

    Zanzalintinib in Osteosarcoma: Balancing Disease Control and Quality of Life

    Philippos A. Costa, MD joins us on OsteoBites to introduce a Phase 2 clinical trial of zanzalintinib for people with osteosarcoma. The study is intended for patients who cannot receive standard chemotherapy or whose cancer has not responded to available treatments. The goal is to explore whether this therapy can control the disease while preserving quality of life during treatment. Philippos A. Costa, MD., is an Oncologist at Yale University. He received his medical degree from the Universiade Federal do Vale do Sao Francisco, Brazil, and completed two internal medicine residencies; at the Universidade Federal de Uberlandia and at the University of Miami Miller School of Medicine, and his fellowship at Yale University. He is an expert in Early Developmental Therapeutics as well as Sarcomas, including osteosarcoma.

    54 min

  7. Apr 3

    Extracellular Matrix Degradation to Overcome Osteosarcoma Chemoresistance

    The Rao Lab at Seattle Children's Research Institute developed a three-dimensional (3D) tissue-engineered model of osteosarcoma to investigate the effects of the extracellular matrix on malignant cell function. The study demonstrated that culturing osteosarcoma (OS) cells within a 3D collagen matrix induced unique cellular responses, altered morphology, enhanced tumorigenic behavior, and reduced chemosensitivity compared to cells cultured in 2D collagen or on standard tissue culture plastic. They identified overexpression of drug efflux pumps as a key mechanism of chemoresistance and further showed that a tyrosine kinase inhibitor could suppress drug efflux activity, thereby enhancing the efficacy of standard chemotherapeutic agents. While this earlier study examined the effects of a single collagen concentration on osteosarcoma phenotype, clinical solid tumors are characterized by altered extracellular microarchitecture, including increased matrix density and stiffness. These changes restrict drug transport and limit chemotherapy-induced cell death. Dr. Rao will present findings from engineered tumor models incorporating varying matrix densities and demonstrate how matrix density influences osteosarcoma function. This work was funded by the 2025 Outsmarting Osteosarcoma Young Investigator Hope Award. Dr. Rao is a Pediatric Hematologist Oncologist at the Seattle Children's Hospital and a Principal Investigator in the Ben Towne Center for Childhood Cancer and Blood Disorders Research at the Seattle Children's Research Institute. His lab harnesses biomaterials and tissue engineering technologies to design 3D models of osteosarcoma to understand how cell-matrix interactions lead to chemoresistance.

    53 min

  8. Mar 27

    Targeting EPHA2 with dual-armored CAR T cells for immunotherapy in pediatric osteosarcoma

    Osteosarcoma Webinar Series: Ali Cihan, PhD, a research scholar at Memorial Sloan Kettering Cancer Center, will discuss his OutSmarting Osteosarcoma funded work on targeting EPHA2 with dual-armored CAR T cells for immunotherapy in pediatric osteosarcoma. Dr. Ali Cihan is a research scholar at Memorial Sloan Kettering Cancer Center, where he focuses on immunotherapy with a particular emphasis on advancing cellular therapies for pediatric solid tumors, including osteosarcoma. He received his Ph.D. from The Rockefeller University, where his research explored how chromosomal abnormalities and transcriptional dysregulation contribute to the development of high-risk pediatric leukemias. Motivated by the urgent need to improve outcomes for children with cancer, especially those facing limited treatment options, Dr. Cihan turned his focus to bridging laboratory discoveries and clinical application. His current work aims to develop immune-based therapeutic strategies that address the unique biological and clinical challenges of pediatric cancers.

    1h 5m
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Each week, MIB Agents talks with the leaders and innovators in osteosarcoma surgery, research, treatment and advocacy. Questions are taken during the webinar and are included in each podcast. More information is available at www.mibagents.org

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