MIB Agents OsteoBites and osTEAo

Results of a phase II trial of olaparib in combination with ceralasertib in patients with recurrent and unresectable osteosarcoma

Osteosarcoma Webinar Series: Katie Janeway, MD and Suzanne Forrest, MD join us on OsteoBites to discuss results of a phase II trial of olaparib in combination with ceralasertib in patients with recurrent and unresectable osteosarcoma.

Dr. Janeway received her MD and MMSc from Harvard Medical School. She completed her pediatrics residency and her Pediatric Hematology-Oncology fellowship at Boston Children’s Hospital and Dana-Farber Cancer Institute. She is an Associate Professor of Pediatrics, a Senior Physician who cares for young people with sarcoma, and Director of Clinical Genomics. Dr. Janeway’s research is focused on precision oncology and bone sarcomas. She leads clinical trials both as an independent investigator and as the Chair of the Children’s Oncology Group (COG) Bone Tumor Committee. The Janeway Laboratory leads several studies, which have enrolled and sequenced more than 2,500 patients with childhood cancers. They are using this data to deepen the understanding of clinical and genomic factors explaining prognosis and treatment response, and resistance, with a focus on sarcomas. In collaboration with Count Me In, the group is innovating patient partnerships in sarcoma research.Dr. Forrest completed her medical school training at Yale University, followed by pediatrics training in the Boston Combined Residency Program. She then pursued a pediatric oncology fellowship at Dana-Farber Cancer Institute / Boston Children’s Hospital. Currently, she serves as an Assistant Professor of Pediatrics at Harvard Medical School and an Attending Physician in the Department of Hematology/Oncology at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Her research focuses on developing novel clinical trials that utilize cancer genomics to guide treatment strategies for pediatric solid tumors.

After a short presentation on this research, they will take questions from attendees. Share your questions in advance with us at [email protected].

Osteosarcoma Webinar Series: Isidro Cortés-Ciriano will discuss his work studying how ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution.

In this episode of osTEAo, Mia and Sammy — joined by Mackenzie and Alejandro — open up about the many forms of loss: losing friends, losing health, and losing parts of themselves as life shifts after cancer. They talk about how grief shows up in changing abilities, in memories, and in the quiet moments where life feels different than before. Through honest conversation about rituals, storytelling, and the ways grief softens over time, they explore how remembrance can heal and how connection helps carry the weight. Despite the heaviness, the group finds hope in shared stories, laughter, and the idea that while grief is intertwined with love, no one has to navigate it alone.

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.

This one’s for anyone who’s ever had a hospital night that felt straight out of a horror movie. In Spooky Sarcoma Stories, four young osteosarcoma survivors — Sammy, Alejandro, Inaaya, and Max swap their wildest, scariest, and most surreal treatment memories, like the time Alejandro thought the IV tower was a robot monster, Max’s feeding tube removal turned into a “murder mystery,” Inaaya woke up to chemo-soaked sheets, and Sammy faced a limb salvage surgery that went sideways. It’s honest, a little dark, sometimes funny, and totally real. Because osteosarcoma doesn’t need ghosts to be spooky.

Osteosarcoma Webinar Series: Alanna Church, MD, Associate Director, Laboratory for Molecular Pediatric Pathology at Boston Children's Hospital, Assistant Professor of Pathology at Harvard Medical School, and Conference Cochair joins us on OsteoBites to discuss insights and higlights from the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer—From Biology to Breakthrough Therapies, September 25-28 in Boston.

Dr. Church is currently a Molecular and Pediatric Pathologist at Boston Children's Hospital, where she is a founder and associate medical director of the Laboratory for Molecular Pediatric Pathology (LaMPP). She is an Assistant Professor of Pathology at Harvard Medical School, the Program Director for the Harvard Molecular Genetic Pathology Fellowship, and the incoming Chair of Clinical Practice for the Association for Molecular Pathology. Her clinical and research work focuses on bringing molecular testing to the clinical care of children with cancer. Through institutional projects (the Profile study, GAIN consortium study), she has profiled thousands of children's tumors and has used these results to make real-time impacts on their diagnoses and treatments. She is involved in national initiatives to improve the quality and access to molecular testing for children with cancer, including the NCI-funded Count Me In Study (Dana Farber, Broad Institute), the National Comprehensive Cancer Network, the National Institutes of Health, and the Children's Oncology Group.

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.

In an inspirational episode of osTEAo, hosts Mia and Sammy honored the memory of their late friend and co-host, Camille Wahl. As one of the original founders of the podcast, Camille envisioned osTEAo as a space where adolescents and young adults affected by osteosarcoma could share their stories and find connection. Her legacy as both a friend and an advocate continues to inspire the mission of the podcast: raising awareness, building community, and reminding young people facing cancer that they are not alone.

Sloane, Mackenzie, and Alejandro joined Mia and Sammy in this episode to reflect on the many ways that pain can be transformed into purpose. Though cancer often brings hardship, survivors and families are finding ways to channel those difficult experiences into advocacy. Whether it’s raising awareness through initiatives like gold bows, supporting efforts to expand access to clinical trials, or simply showing up for someone in treatment, each act of advocacy helps strengthen the community and spark positive change.

Much of the conversation centered on the power of sharing stories and small acts of advocacy. Speaking honestly about the cancer experience helps others feel seen and understood, and even the smallest gestures can make a meaningful difference. These simple, everyday actions remind us that advocacy isn’t only about big campaigns or policy change. It's also about kindness, connection, and making sure no one feels alone.

In the end, the episode was both a tribute and a reminder of what matters most: community, compassion, and hope. Camille’s vision shines through in every story shared and every effort to make things better for others. Even in the face of loss, the osTEAo team showed how pain can be carried forward with love and turned into something purposeful.

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.