- |||||||||| Precision medicine: Novel PI3K inhibitor as cancer treatment. () - Apr 28, 2022 - Abstract #ASCO2022ASCO_5266;
A 9-residue variant ranging from amino acids 6Lys to 14Gln showed the most promise and will be used in future studies to reformulate Selectide-18. Being half the size of Selectide-18, this optimized drug is anticipated to have improved cell permeability without sacrificing inhibitory function.
- |||||||||| Piqray (alpelisib) / Novartis
Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations. (Available On Demand; 329) - Apr 28, 2022 - Abstract #ASCO2022ASCO_1336; Given the high prevalence of CRC in the United States and worldwide this represents a clinically meaningful prevalence of multi-hit PIK3CA. Future investigation on the clinical utility of PI3K inhibitors may be warranted in multi-hit PIK3CA CRC.
- |||||||||| Piqray (alpelisib) / Novartis
Characterization of alpelisib-associated hyperglycemia in metastatic breast cancer. (Available On Demand; 394) - Apr 28, 2022 - Abstract #ASCO2022ASCO_1100; Overweight BMI and hemoglobin A1c in the prediabetes or diabetes range were strongly predictive of developing alpelisib-associated hyperglycemia. Management of these co-morbidities prior to alpelisib treatment should be strongly considered.
- |||||||||| Piqray (alpelisib) / Novartis
Journal: Management of Phosphatidylinositol-3-Kinase Inhibitor-Associated Hyperglycemia. (Pubmed Central) - Apr 26, 2022 Clinical studies show that alpelisib-associated hyperglycemia is reversible and manageable, rarely leading to treatment discontinuation. Management of PI3Ki-associated hyperglycemia in patients with breast cancer should focus on the prevention of acute and subacute complications of hyperglycemia, allowing patients to remain on anticancer treatment longer.
- |||||||||| Mekinist (trametinib) / Novartis, taselisib (GDC-0032) / Roche, Cotellic (cobimetinib) / Exelixis, Roche
Journal: Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis. (Pubmed Central) - Apr 26, 2022 Imaging mass cytometry of human pGVHD revealed that T cells around bronchioles were positive for phosphorylated ERK, while B cells were positive for phosphorylated AKT. Thus, perivascular inflammation and bronchiolitis mediated by activation of the MEK/ERK and PI3K/AKT pathways are essential for pGVHD and represent a potential novel therapeutic target in humans.
- |||||||||| mosunetuzumab (RG7828) / Roche, Biogen
Mosunetuzumab Monotherapy is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory Follicular Lymphoma who have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study (Exchange Auditorium) - Apr 25, 2022 - Abstract #BSH2022BSH_27; P1/2 Mosun had a manageable safety profile; C1 step-up dosing mitigated CRS, enabling treatment without mandatory hospitalisation. 3L+R/R FL, pts with relapsed/refractory follicular lymphoma who have received ≥2 prior therapy lines; Ab, antibody; CI, confidence interval; CR, complete response; ORR, objective response rate; PET/CT, positron emission tomography/computed tomography; POD24, progression of disease within 24 months from the start of initial therapy; pts, patients.
- |||||||||| Ibrance (palbociclib) / Pfizer
Review, Journal: A comprehensive review on anticancer mechanism of bazedoxifene. (Pubmed Central) - Apr 22, 2022 In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets and anticancer mechanism of BZA which may help the further design and conduct of research and repositioning it for oncological clinic trials.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Glucosamine enhances proliferation, barrier, and anti-oxidative functions in porcine trophectoderm cells. (Pubmed Central) - Apr 22, 2022 The addition of 0.25 mmol L GlcN enhanced the phosphorylation of mTOR signaling proteins, which can be inhibited by the inhibitor of phosphatidylinositol 3-kinase (PI3K), LY294002...The addition of 0.5 mmol L GlcN increased the protein expression of zonula occludens-3 (ZO-3), claudin-3, and claudin-4 in pTr cells, while inhibited the downregulation protein of claudin-1 and claudin-3 brought about by oxidative stress. Collectively, GlcN plays an important role in promoting proliferation and stimulating the mTOR cell signaling pathway, as well as ameliorating oxidative stress and augmenting barrier functions in pTr cells.
- |||||||||| Journal: Design, synthesis and bioactivities evaluation of novel oleanolic acid derivatives as potent PI3K inhibitors. (Pubmed Central) - Apr 22, 2022
The results suggested that attachment of additional structural elements such as association of thiazole group to A ring and insertion of phenylurea group was important for increasing activities. The most active derivative was compound II, which exhibited PI3K inhibitory activity (IC = 58.42 nmol/l) and improved interaction with activity site of PI3K according with docking studies.
- |||||||||| The Evolving Landscape of HR+/HER2- Breast Cancer Treatment (RM 1(Vista 1+2)) - Apr 22, 2022 - Abstract #GBCC2022GBCC_84;
Among post-menopausal women, improvement in progression-free survival has been observed with all 3 CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) with aromatase inhibitor as 1st line therapy, and improvement in overall survival improvement with endocrine therapy and ribociclib in both pre-menopausal and post-menopausal HR+ MBC...Pivotal results from SOLAR-1 demonstrated that the PI3Kα-selective inhibitor alpelisib is associated with improved clinical outcomes, and alpelisib is the first PI3K inhibitor approved in breast cancer and is the only therapy for ABC that specifically targets the effects of PIK3CA mutations...In addition, there have been number of oral SERDs in clinical development for metastatic ER+ breast cancer. In this presentation, we will review the current guidelines latest developments in management of HR+/HER2- breast cancer.
- |||||||||| chlorpromazine / Generic mfg.
Journal: Presenilin 2 N141I mutation induces hyperactive immune response through the epigenetic repression of REV-ERBα. (Pubmed Central) - Apr 21, 2022 The antipsychotic chlorpromazine restores the REV-ERBα level by normalizing DNA methylation through the inhibition of PI3K/AKT1 pathway, and prevents the overexcitation of innate immune cells and cognitive decline in KI/+ mice. These results highlight a pathogenic link between this AD mutation and immune cell overactivation through the epigenetic suppression of REV-ERBα.
- |||||||||| Opdivo (nivolumab) / BMS, Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Trial completion date, Trial primary completion date, Combination therapy, IO biomarker, Metastases: Duvelisib in Combination With Nivolumab in Patients With Advanced Unresectable Melanoma (clinicaltrials.gov) - Apr 21, 2022 P1/2, N=42, Recruiting, These results highlight a pathogenic link between this AD mutation and immune cell overactivation through the epigenetic suppression of REV-ERBα. Trial completion date: Jan 2024 --> Oct 2027 | Trial primary completion date: Aug 2022 --> Apr 2025
- |||||||||| Piqray (alpelisib) / Novartis
ALPELISIB FOR THE TREATMENT OF PROS: RESPONSE RATE BY IMPUTATION IN EPIK-P1 () - Apr 20, 2022 - Abstract #ASPHO2022ASPHO_67; When considered with the ~74% of patients who observed any reduction in lesion volume, these data strongly speak to the meaningful clinical benefit alpelisib may provide patients with PROS. Supported by Novartis Pharmaceuticals Corporation.
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