SDHB deficient

Follow-up revealed metastasis in 1 patient, leading to mortality. Our findings broaden the morphologic spectrum and highlight a new point mutation in the SDHB gene, providing a genetic change spectrum for this tumor entity.

Treatments by the SDH inhibitor fluopyram revealed that the SDH complex carrying the R244H mutation in subunit B displayed residual SDH activity, which was also confirmed by our structural analyses. We also observed a link between dopaminergic neuronal health and SDHB-1.

We were treating the human pheochromocytoma cell line (hPheo1) with knocked down SDHB using radiation, GDH inhibitor "R162" and PARP inhibitor "Olaparib"...These results suggested that enhancing radiation-induced DNA damage could be a potential treatment strategy for metastatic pheochromocytomas/paragangliomas. Inhibiting GDH1 and PARP activities, with radiation, may represent promising strategies for the treatment of SDHB deficient pheochromocytoma/paraganglioma; however, their effects do not appear to be specific to SDHB-deficient cells and require further validation.

These findings highlight the value of genetically engineered, tissue-specific murine models in predicting immunotherapy outcomes in rare cancers. Moreover, they support the therapeutic potential of MBTA for treating SDHB-deficient renal cell carcinoma and provide a rationale for further translational studies.

Rapid metastatic relapse after subtotal gastrectomy was resistant to imatinib. The patient received four cycles of cisplatin, etoposide, and pembrolizumab followed by pembrolizumab maintenance with a complete response...Pembrolizumab is still in maintenance with no relapse to date. The role of chemoimmunotherapy as part of treatment in recurrent metastatic SDH-deficient, PDL1-positive GIST patients is worth further investigation.

Two mechanisms of acquired resistance to DNA alkylating chemotherapies are identifiable; MGMT overexpression and mismatch repair-deficiency causing hypermutation. Our comprehensive multi-omic analysis of SDHB-mutant PCPG therefore identifies features of metastatic disease and treatment response, expanding our understanding of these rare neuroendocrine tumours.

Our analyses suggested that SDHB-deficient PPGL exhibited a higher incidence of relapse. Furthermore, M2 macrophage infiltration in TME might be crucial in pseudohypoxic PPGL pathogenesis.