ArticleCell death & disease2020
Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- FOXM1 inhibitor, RCM‑1, enhances venetoclax mediated apoptosis through downregulation of ATP2B4 in rhabdomyosarcoma.International journal of oncology · 2026Article
- Article
- HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.Cell death and differentiation · 2025Article
- Novel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer.Cell death & disease · 2025Article
- Disrupting resistance: novel therapeutic approaches to combat multidrug resistance in fusion-negative rhabdomyosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo.BMC cancer · 2024Article
- Quantitative systems pharmacology modeling of tumor heterogeneity in response to BH3-mimetics using virtual tumors calibrated with cell viability assays.CPT: pharmacometrics & systems pharmacology · 2024Article
- The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance.Cell death & disease · 2023Article
- The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma.Cancers · 2023Article
- BBB-on-a-chip with integrated micro-TEER for permeability evaluation of multi-functionalized gold nanorods against Alzheimer's disease.Journal of nanobiotechnology · 2023Article
- B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease.Exploration of targeted anti-tumor therapy · 2023Review
- Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy.NPJ precision oncology · 2022Article
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.Cell death & disease · 2022Review
- Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics.Cancer discovery · 2022Review
- The E3 Ubiquitin Ligase Fbxo4 Functions as a Tumor Suppressor: Its Biological Importance and Therapeutic Perspectives.Cancers · 2022Review
- MEK and MCL-1 sequential inhibition synergize to enhance rhabdomyosarcoma treatment.Cell death discovery · 2022Article
- Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL.Leukemia · 2022Article
- Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers.Biochemical Society transactions · 2021Review
- Fatty acid synthase (FASN) regulates the mitochondrial priming of cancer cells.Cell death & disease · 2021Article
- MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. Refractory/relapsed RMS patients present a bad prognosis that combined with the lack of specific biomarkers impairs the development of new therapies. Here, we utilize dynamic BH3 profiling (DBP), a functional predictive biomarker that measures net changes in mitochondrial apoptotic signaling, to identify anti-apoptotic adaptations upon treatment. We employ this information to guide the use of BH3 mimetics to specifically inhibit BCL-2 pro-survival proteins, defeat resistance and avoid relapse. Indeed, we found that BH3 mimetics that selectively target anti-apoptotic BCL-xL and MCL-1, synergistically enhance the effect of clinically used chemotherapeutic agents vincristine and doxorubicin in RMS cells. We validated this strategy in vivo using a RMS patient-derived xenograft model and observed a reduction in tumor growth with a tendency to stabilization with the sequential combination of vincristine and the MCL-1 inhibitor S63845. We identified the molecular mechanism by which RMS cells acquire resistance to vincristine: an enhanced binding of BID and BAK to MCL-1 after drug exposure, which is suppressed by subsequently adding S63845. Our findings validate the use of DBP as a functional assay to predict treatment effectiveness in RMS and provide a rationale for combining BH3 mimetics with chemotherapeutic agents to avoid tumor resistance, improve treatment efficiency, and decrease undesired secondary effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.