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. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. MAR 13

    Identifying mechanisms of chemoresistance in metastatic osteosarcoma using molecular barcoding

    Dr. Aafrin Pettiwala from UCSF joins us on OsteoBites to discuss her OutSmarting Osteosarcoma funded work on identifying mechanisms of chemoresistance in metastatic osteosarcoma using molecular barcoding. The presentation covers how intratumoral heterogeneity drives chemoresistance and metastasis in osteosarcoma by using lineage tracing (CaTCH) and patient-derived xenograft models. She has identified resistant and metastatic cell subpopulations and their molecular vulnerabilities, and further research seeks to uncover new therapeutic targets to improve treatment outcomes for metastatic osteosarcoma patients. Dr. Pettiwala earned her PhD in Cancer Biology from Institut Curie in Paris, France, where she studied therapeutic resistance and phenotypic plasticity in brain tumors. Her doctoral work focused on uncovering the molecular mechanisms that allow cancer cells to adapt and evade treatment. Currently, Aafrin is a postdoctoral researcher in the lab of Dr. Alejandro Sweet-Cordero at the University of California, San Francisco (UCSF). Her research centers on understanding chemotherapy resistance in metastatic osteosarcoma, with an emphasis on clonal dynamics, tumor evolution, and lineage tracing using high-throughput barcoding technologies.

    59 min

  7. MAR 6

    New insights into shared molecular and genomic features between humans and dogs with OS

    Amy LeBlanc, DVM, a board-certified veterinary oncologist, Senior Scientist, and the Director of the intramural NCI’s Comparative Oncology Program, will review canine osteosarcoma and the clinical, biologic, and molecular features that make it a relevant animal-patient model for humans. She will share new data from the NCI's Comparative Oncology Program regarding MYC, and its value as a predictive biomarker for the disease in canine patients. Dr. Amy LeBlanc is a board-certified veterinary oncologist, Senior Scientist, and the Director of the intramural NCI’s Comparative Oncology Program. In this position, she conducts preclinical mouse and translational pet dog studies that are designed to inform the drug and imaging agent development path for human cancer patients, specifically those with osteosarcoma. She directly oversees the NCI Comparative Oncology Trials Consortium (COTC), which provides the infrastructure necessary to connect participating veterinary academic institutions with stakeholders in drug development to execute fit-for-purpose comparative clinical trials in novel therapeutics and imaging agents. Her program provides support to several extramural NCI-funded initiatives, including the Integrated Canine Data Commons and Cancer Moonshot-funded canine immunotherapeutic clinical trials conducted under the PRECINCT network.

    1h 10m

  8. FEB 27

    Implementing personalized, adaptive therapies in osteosarcoma

    Osteosarcoma Webinar Series: Corey Weistuch, PhD, an Assistant Attending Physicist in the Service for Predictive Informatics within the Department of Medical Physics at Memorial Sloan Kettering Cancer Center, will discuss his OutSmarting Osteosarcoma funded work on implementing personalized, adaptive therapies in osteosarcoma. Corey Weistuch, PhD, is an Assistant Attending Physicist in the Service for Predictive Informatics within the Department of Medical Physics at Memorial Sloan Kettering Cancer Center. His work is focused on developing mathematical models to understand cancer development, progression, and metastasis by integrating multimodal data. Central to this approach is the recognition that tumors occupy a finite spectrum of functional states, each characterized by distinct treatment sensitivities and metastatic tendencies that evolve over time and in response to therapy. His research centers on two primary objectives: 1) developing innovative mathematical tools to identify cancer phenotype drivers, and 2) precision modeling of cancer evolution and site-specific metastatic dissemination. By leveraging his interdisciplinary training in mathematics and biology, he collaborates closely with experimental biologists and clinicians to ensure that his computational predictions are effectively translated into tangible clinical applications and trials. The Weistuch Lab's work aims to validate targeted drug candidates for osteosarcoma (OS) using patient-derived xenograft (PDX) models, leveraging a newly developed atlas of OS transcriptional states, called archetypes, to guide personalized, adaptive treatment strategies. By testing archetype-specific therapies in different disease phases, they establish a foundation for precision-based clinical trials, ultimately with the goal of improving outcomes for patients with advanced or refractory OS.

    1h 2m
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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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