- |||||||||| Review, Journal: PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. (Pubmed Central) - Aug 23, 2023
In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.
- |||||||||| Tevimbra (tislelizumab-jsgr) / BeiGene, Brukinsa (zanubrutinib) / BeiGene, BGB-10188 / BeiGene
Trial completion date, Combination therapy, Monotherapy: BGB-A317-3111-10188-101: Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab (clinicaltrials.gov) - Aug 23, 2023 P1/2, N=126, Recruiting, activity by alpelisib can hinder the inflammatory response and infiltration of immune cells occurring by APAP-hepatotoxicity. Trial completion date: Nov 2025 --> Feb 2025
- |||||||||| adavosertib (AZD1775) / AstraZeneca, TheraCIM (nimotuzumab) / Daiichi Sankyo, Oncoscience, Biocon
Journal: Combined Wee1 and EGFR inhibition reveals synergistic antitumor effect in esophageal squamous cell carcinoma. (Pubmed Central) - Aug 21, 2023 In conclusion, our work uncovers that EGFR-mAb Nimotuzumab combined with Wee1 inhibitor AZD1775 elicited potentiated anticancer activity against ESCC cell line and PDXs partially through PI3K/Akt and MAPK pathways blockade. These pre-clinical data raise the promising that ESCC patients may benefit from dual target EGFR and Wee1.
- |||||||||| LY294002 / Eli Lilly
Journal: Regulation of FGF2-induced proliferation by inhibitory GPCR in normal pituitary cells. (Pubmed Central) - Aug 18, 2023 These results suggest the potential for developing PI3K inhibitors as a therapeutic option for these patients. Anterior pituitary primary cell cultures from Wistar female rats were treated with FGF2 (10ng/mL) or somatostatin analog (SSTa, 100nM) alone or co-incubated with or without the inhibitors of GPCR-G?i, pertussis toxin (PTX, 500nM), MEK inhibitor (U0126, 100
- |||||||||| Review, Journal: Inhibitors of the PI3K/AKT/mTOR pathway in human malignancies; trend of current clinical trials. (Pubmed Central) - Aug 18, 2023
Following the extraction of the data, finally we analyzed 2250 included studies in multiple steps, beginning with an overview and moving on to the details about type of malignancies, inhibitors, and treatment strategies. We also took a closer look at more than 100 phase III-IV clinical trials to pinpoint promising therapies, hoping that presenting a comprehensive picture of current clinical trials casts a flash of light on what remains to be done in future clinical trials of PI3K/AKT/mTOR inhibitors in human malignancies.
- |||||||||| Journal: Discovery of a Novel Photocaged PI3K Inhibitor Capable of Real-Time Reporting of Drug Release. (Pubmed Central) - Aug 16, 2023
A novel photocaged PI3K inhibitor 2 was designed and synthesized by introducing a cascade photocaging group to block its key interaction with the kinase. Upon UV light irradiation, the photocaged compound released a highly potent PI3K inhibitor to recover its anticancer properties and a fluorescent dye for real-time reporting of drug release, providing a new approach for studying the PI3K signaling transduction pathway as well as developing precisely controlled cancer therapeutics.
- |||||||||| Piqray (alpelisib) / Novartis, sotrastaurin (AEB071) / Novartis
Trial completion, Combination therapy, Metastases: Trial of AEB071 in Combination With BYL719 in Patients With Melanoma (clinicaltrials.gov) - Aug 15, 2023 P1, N=30, Completed, All these findings support CXHO as a promising drug for the treatment of GC. Unknown status --> Completed
- |||||||||| Imbruvica (ibrutinib) / AbbVie, J&J
Curcumin enhances ibrutinib induced killing effect against TP53-mutated Chronic Lymphocytic Leukemia cells in vitro () - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_229; Our findings highlight the importance of longitudinal genomic monitoring to uncover evolving mutational profiles and their clinical implications. (1) Ibrutinib combined with curcumin has synergistic killing effect on TP53- mutated CLL cells; (2) Curcumin increases the killing effect of ibrutinib on TP53-mutated CLL cells by inhibiting PI3K and NF?B pathway, and degrading p53mt protein.
- |||||||||| sirolimus / Generic mfg.
Journal: Thymoquinone induces apoptosis and protective autophagy in gastric cancer cells by inhibiting the PI3K/Akt/mTOR pathway. (Pubmed Central) - Aug 14, 2023 Furthermore, TQ decreased the phosphorylation levels of phosphatidylinositol-4,5-bisphosphate 3 kinase (PI3K), protein kinase B (Akt), and mechanistic target of rapamycin (mTOR)...TQ inhibits the proliferation of GC cells and induces apoptosis and protective autophagy by inhibiting the PI3K/Akt/mTOR pathway. The results suggest that the combination of TQ and autophagy inhibitors might be a potential chemotherapeutic strategy for GC.
- |||||||||| Orserdu (elacestrant) / Menarini
Biomarker, Journal, Circulating tumor DNA: Circulating tumor DNA in breast cancer: a biomarker for patient selection. (Pubmed Central) - Aug 12, 2023 Liquid biopsy for ctDNA detection represents an exciting new field in rapid evolution. Several trials are ongoing to validate the clinical utility of ctDNA in daily practice in the early setting and to expand its current indications in the metastatic one.
- |||||||||| Journal: Combination strategies to overcome drug resistance in FLT acute myeloid leukaemia. (Pubmed Central) - Aug 12, 2023
This study suggests that a multi-targeted intervention involving a CDK4/6 inhibitor with a FLT3 inhibitor or a pan-PI3K inhibitor might be a valuable therapeutic strategy for AML to overcome drug resistance. Moreover, many patients cannot tolerate high doses of the drugs that were studied (quizartinib, palbociclib and PI3K inhibitors) for longer periods, and it is therefore of high significance that the drugs act synergistically and lower doses can be used.
- |||||||||| Monjuvi (tafasitamab-cxix) / Incyte, parsaclisib (INCB50465) / Incyte
Enrollment change, Combination therapy, Pan tumor: topMIND: A Study Evaluating Safety, PK, and Efficacy of Tafasitamab and Parsaclisib in Participants With Relapsed/Refractory Non Hodgkin Lymphoma (R/R NHL) or Chronic Lymphocytic Leukemia (CLL) (clinicaltrials.gov) - Aug 8, 2023 P1b/2a, N=54, Active, not recruiting, ANGPTL8 may be a novel therapeutic target against pathological hypertension and hypertensive cardiovascular hypertrophy. N=100 --> 54
- |||||||||| LY294002 / Eli Lilly
Journal: Role of KLF4/NDRG1/DRP1 axis in hypoxia-induced pulmonary hypertension. (Pubmed Central) - Aug 7, 2023 The relationship between NDRG1 and DRP1 and the PI3K/Akt/mTOR pathway was further evaluated by adding mdivi-1 (DRP1 inhibitor) or LY294002 (PI3K inhibitor)...Further, we showed that KLF4 regulated the proliferation and migration of hypoxia-treated hPASMCs via NDRG1. These results indicated a link between KLF4, NDRG1, and DRP1 for the first time, providing new ideas for treating hypoxic pulmonary hypertension.
- |||||||||| nifedipine immediate release / Generic mfg.
Journal: Calcium handling coupled to the endothelin ET and ET receptor-mediated vasoconstriction in resistance arteries: Differential regulation by PI3K, PKC and RhoK. (Pubmed Central) - Aug 5, 2023 Vasoconstriction induced by ET-1 was largely dependent on activation of canonical transient receptor potential channel 3 (TRPC3) and extracellular Ca influx through nifedipine-sensitive voltage-dependent Ca channels...RhoK was a major determinant of the enhanced sensitivity of the contractile filaments underlying ET-1 vasoconstriction, with also a modulatory positive action on Ca influx and intracellular Ca release. Augmented RhoK and PKC activities are involved in vascular dysfunction in hypertension and vascular complications of insulin-resistant states, and these kinases are thus potential pharmacological targets in vascular diseases in which the ET pathway is impaired.
- |||||||||| Journal: CCNI2 promotes pancreatic cancer through PI3K/AKT signaling pathway. (Pubmed Central) - Aug 4, 2023
Moreover, the addition of phosphatidylinositol 3-kinase (PI3K) inhibitors could partially reverse the promoting effect of CCNI2 on the malignant phenotypes of pancreatic cancer cells. CCNI2 promoted pancreatic cancer through PI3K/protein kinase B (AKT) signaling pathway, indicating its potential as a prognostic marker and therapeutic target for pancreatic cancer.
- |||||||||| LY294002 / Eli Lilly
Journal: The roles of stress-induced premature senescence and Akt/FoxO1 signaling in periapical lesions. (Pubmed Central) - Aug 2, 2023 This study enhanced the amount and accuracy of compounds of CLDM and provided new insights into CLDM preventing and treating ALI. Our data indicated that senescence is present in clinical periapical lesions, and Akt/FoxO1 signaling is involved in the H O -induced cellular senescence, which could serve as a potential therapeutic target.
- |||||||||| Piqray (alpelisib) / Novartis
Journal: Characteristics of PIK3CA gene mutations in Her2-low breast cancer (Pubmed Central) - Aug 2, 2023 Statistically significant increase in the frequency of exon 9 mutations of the PIK3CA gene is specific for the group of patients with Her2-low BC. Our results supported the concept of Her2-low BCs as the unique entity and pointed out the need of their further study.
- |||||||||| volasertib (NBL-001) / Oncoheroes, Notable Labs
Journal: Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma. (Pubmed Central) - Jul 31, 2023 To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma...Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.
- |||||||||| Preclinical, Journal: In vitro differentiated human CD4 T cells produce hepatocyte growth factor. (Pubmed Central) - Jul 31, 2023
Furthermore, pharmacological inhibition of PI3K or mTOR was found to inhibit HGF mRNA and protein, while an Akt inhibitor was found to increase these levels. The findings suggest that HGF producing T cells could play a role in disease where Th1 are present.
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