Grumpy-XL schreef op 3 april 2022 23:55:
Dit artikel geeft een vrij recent overzicht van de stand van zaken mbt deze groep geneesmiddelen.
“ PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects” -
www.mdpi.com/1422-0067/22/7/3464/htmLeniolisib wordt hierin ook besproken . Positief is dat leniolisib als “well tolerated” wordt beschouwd .
“ The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted.”
“ 4.15. Leniolisib/CDZ173
Leniolisib/CDZ173 is a potent and selective PI3Kd inhibitor. Most of the studies using Leniolisib are sponsored by Novartis Pharmaceuticals. Although no studies are known in cancer but it is implicated in immunodeficiency disorders such as activated PI3Kd syndrome/p110d-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (APDS/PASLI) where it has been tested in phase II/III trials. Rao et al. have shown that treatment with Leniolisib resulted in dose-dependent inhibition of PI3Kd pathway hyperactivation in cells expressing APDS-causative p110d variants and in T-cell blasts derived from patients. In addition it was shown that oral administration of Leniolisib in six APDS patients resulted in dose-dependent inhibition of the PI3K/AKT pathway evaluated via ex vivo assay and had enhanced immune dysregulation. Thus, Leniolisib is known to be well tolerated and has improved laboratory and clinical parameters in patients with APDS, supporting the specific inhibition of PI3Kd as a promising new targeted therapy in patients with APDS and other diseases characterized by hyperactivation of the PI3Kd pathway [309].
Leniolisib is also tested in patients with primary sjögren’s syndrome (PSS) in phase II trials where its oral administration resulted in inhibition of phosphorylated AKT in ex vivo stimulated B cells, decreased the serum CXCL13 levels and reduced the frequency of circulating follicular T helper-like cells ”