Year: 2026
Type: article
Abstract: PIKfyve inhibition creates a de novo lipogenesis dependency in MM as observed in PDAC and whether combining PIKfyve blockade with MAPK pathway inhibitors can exploit this vulnerability.In conclusion, Bonolo de Campos et al report an elevated dependence on PIKfyve-driven lysosomal processes in MM and identify selective PIKfyve inhibitors to be exploited as next-generation therapies in MM.Although PIKfyve inhibition has been explored in other cancers, with agents such as apilimod and ESK981 already in clinical development, this study moves the field forward by providing a detailed multiomic dissection of PIKfyve biology in myeloma and unveiling a new class of selective inhibitors with favorable pharmacological and safety profiles.Importantly, their work links PIKfyve inhibition to both direct tumor cell killing as well as metabolic and immune remodeling, opening multiple avenues for synergy (see figure).Together, these findings position PIKfyve inhibition as a credible next-generation strategy in myeloma and a promising platform for rational combination therapies.Conflict-of-interest disclosure: M.F.declares no competing financial interests.
Source: Blood
Authors: Anna Skwarska, Marina Konopleva
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7127898877