- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] EX VIVO DRUG SENSITIVITY IDENTIFIES COMBINATION TREATMENT WITH PI3K/BCL-2 INHIBITORS FOR MONOTHERAPY-REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA () - May 13, 2021 - Abstract #EHA2021EHA_1228; Background The phosphatidylinositol 3-kinase inhibitors (PI3Ki) idelalisib and duvelisib are approved for relapsed chronic lymphocytic leukemia (CLL)...However, treatment with the p110d-selective PI3Ki umbralisib plus venetoclax showed more selective targeting of CLL cells compared to normal B cell and T cells than combinations involving a pan-PI3Ki...Drug sensitivity assessment of an ibrutinib (BTK inhibitor), idelalisib and venetoclax refractory CLL patient indicated combination of idelalisib and venetoclax as a promising therapeutic option...Interestingly, the patient continued to show a strong ex vivo response to the pan-PI3K inhibitors buparlisib, copanlisib and pictilisib, suggesting that these therapies may be considered for CLL patients who relapse on currently available targeted therapies...This demonstrates that ex vivo drug sensitivity assessments can guide clinical decisions in CLL. We further showed that CLL cells from refractory patients remain sensitive to pan-PI3Ki ex vivo, suggesting pan-PI3Ki as potential treatment options to be explored for relapsing CLL patients.
- |||||||||| pirtobrutinib (LOXO-305) / Eli Lilly
[VIRTUAL] PIRTOBRUTINIB (LOXO-305), A NEXT GENERATION, HIGHLY SELECTIVE, NON-COVALENT BTK INHIBITOR IN PREVIOUSLY TREATED RICHTER TRANSFORMATION: RESULTS FROM THE PHASE 1/2 BRUIN STUDY () - May 13, 2021 - Abstract #EHA2021EHA_1074; P1/2 Prior RT directed therapies included chemoimmunotherapy (100%, n=9), covalent BTKi (44%, n=4), anti-PD-1 or PD-L1 antibody (33%, n=3), mTOR inhibitor (22%, n=2), PI3K inhibitor (22%, n=2), CAR-T cell therapy (n=1), autologous stem cell transplant (n=1), polatuzumab vedotin (n=1), and pomalidomide (n=1)...Updated data with additional follow-up in all 17 RT pts will be presented. Conclusion Pirtobrutinib showed promising initial efficacy in pts with pretreated RT with extremely poor prognosis, including in pts who had received prior chemoimmunotherapy and covalent BTK inhibitors.
- |||||||||| Journal: LINC01198 facilitates gliomagenesis through activating PI3K/AKT pathway. (Pubmed Central) - May 13, 2021
Finally, we further verified that LINC01198 hindered glioma tumour growth in vivo through AKT-dependent manner. Jointly, LINC01198 activates PI3 K/AKT signalling to exert oncogenic function in gliomagenesis by regulating PIK3CA and PTEN, which highlights a new approach for glioma treatment.
- |||||||||| Journal: Cadmium induces apoptosis of pig lymph nodes by regulating the PI3K/AKT/HIF-1α pathway. (Pubmed Central) - May 13, 2021
Cd can significantly reduce the expression of PI3K, AKT and HIF-1α in the three lymph nodes. In summary, Cd induces oxidative stress and regulates the PI3K/AKT/HIF-1α signal transduction pathway to cause mitochondrial dynamics disorder, which leads to the apoptosis of pig lymph nodes, suggesting that Cd-induced mitochondrial pathway apoptosis is related to Cd pig lymph nodes play an important role in the toxicity mechanism.
- |||||||||| Jakafi oral (ruxolitinib) / Novartis, Incyte, parsaclisib (INCB50465) / Incyte
[VIRTUAL] A phase 3, randomized, double-blind, placebo- controlled study of ruxolitinib plus parsaclisib in patients with JAK- and PI3K-inhibitor treatment–naıve myelofibrosis () - May 12, 2021 - Abstract #BSH2021BSH_336; P3 Secondary objectives include evaluation and comparison of patient-reported MF symptoms, overall survival, time to onset and duration of response in spleen volume, and safety and tolerability for ruxolitinib plus parsaclisib versus ruxolitinib plus placebo. Sites are opening across the US, Canada, EU, and Asia.
- |||||||||| Jakafi oral (ruxolitinib) / Novartis, Incyte, parsaclisib (INCB50465) / Incyte
[VIRTUAL] A randomized, double-blind, placebo-controlled phase 3 study of parsaclisib plus ruxolitinib in patients with myelofibrosis who have suboptimal response to ruxolitinib () - May 12, 2021 - Abstract #BSH2021BSH_331; P3 Sec- ondary objectives are to evaluate and compare the effect of add-on parsaclisib versus placebo on: patient-reported MF symptoms, overall survival, time to onset and duration of spleen volume response, and safety and tolerability. Sites are opening throughout the US, EU, China, and Japan.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats. (Pubmed Central) - May 12, 2021 Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3β pathway.
- |||||||||| Journal: Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway. (Pubmed Central) - May 12, 2021
In conclusion, the findings of the present study indicated that Runx2 silencing in HKFs might significantly inhibit the cell proliferation, migration and the expression levels of ECM‑related proteins, and promote apoptosis via suppressing the PI3K/AKT signaling pathway. Thus, Runx2 siRNA treatment may reverse the pathological phenotype of keloids through the inhibition of PI3K/AKT signaling in patients.
- |||||||||| MEN1611 / Menarini
Trial completion date, Trial primary completion date, Metastases: B-PRECISE-01: MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer (clinicaltrials.gov) - May 12, 2021 P1, N=48, Recruiting, Ultimately, we show that HER3 inhibition and PD-1 blockade may provide a multimodal precision immunotherapeutic approach for PIK3CA wild type HNSCC, aimed at achieving durable cancer remission. Trial completion date: Jul 2020 --> Jul 2022 | Trial primary completion date: Jul 2020 --> Jul 2022
- |||||||||| Preclinical, Journal: A high-fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice. (Pubmed Central) - May 11, 2021
Similarly, fatty acids but not ketone bodies inhibited glucose uptake, glycolysis, and senescence in SIRT6 knockout fibroblasts, whereas PI3K inhibition antagonized the effects of a high-fatty-acid medium in vitro. Overall, the high-fat diet dramatically reverses numerous consequences of SIRT6 deficiency through modulation of insulin and IGF1 signaling, providing a new basis for elucidation of SIRT6 and fatty-acid functions and supporting novel therapeutic approaches against metabolic disorders and aging-related diseases.
- |||||||||| Zydelig (idelalisib) / Gilead, Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Journal: Managing toxicities of phosphatidylinositol-3-kinase (PI3K) inhibitors. (Pubmed Central) - May 11, 2021 Data on pretreatment considerations, toxicity management, and drug rechallenge are presented. In addition, next-generation PI3K inhibitors and novel treatment approaches with PI3K inhibitors, including combinations, time-limited treatments, and intermittent dosing, are highlighted.
- |||||||||| Adcetris (brentuximab vedotin) / Seagen, Takeda
Review, Journal: Novel targeted therapies of T cell lymphomas. (Pubmed Central) - May 11, 2021 In this review, we present new therapies and current clinical and preclinical trials on targeted treatments for TCL using histone deacetylase inhibitors (HDACi), antibodies, chimeric antigen receptor T cells (CARTs), phosphatidylinositol 3-kinase inhibitors (PI3Ki), anaplastic lymphoma kinase inhibitors (ALKi), and antibiotics, used alone or in combinations. The recent clinical success of ALKi and conjugated anti-CD30 antibody (brentuximab-vedotin) suggests that novel therapies for TCL can significantly improve outcomes when properly targeted.
- |||||||||| Journal: P110α and P110δ catalytic subunits of PI3 kinase regulate lysophosphatidylcholine-induced TRPC6 externalization. (Pubmed Central) - May 11, 2021
Down-regulation of the p110α and p110δ isoforms, but not the p110β or p110γ isoforms, with small interfering RNA significantly decreased phosphatidylinositol (3,4,5)-trisphosphate production and TRPC6 externalization, and significantly improved EC migration in the presence of lysoPC. These results identify an additional role of p110α in EC and reveal for the first time a specific role of p110δ in EC, providing a foundation for subsequent in vivo studies to investigate the impact of p110 isoform inhibition on arterial healing after injury.
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