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  • ||||||||||  Talzenna (talazoparib) / Pfizer
    Journal, BRCA Biomarker, PARP Biomarker:  Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer. (Pubmed Central) -  May 25, 2023   
    To explore treatments to overcome resistance, in vitro studies with TLZ sensitive and resistant ascites-derived murine cell lines were carried out and demonstrated that ATR inhibitor and PI3K inhibitor could be used in combination with the InCeT-TLZ to overcome acquired PARPi resistance. Compared to intraperitoneal PARPi injection, the InCeT-TLZ better inhibits tumor growth, delays the ascites formation, and prolongs the overall survival of treated mice, which could be a promising therapy option that benefits thousands of women diagnosed with ovarian cancer.
  • ||||||||||  Journal:  Activation of Sestrin2 accelerates deep second-degree burn wound healing through PI3K/AKT pathway. (Pubmed Central) -  May 24, 2023   
    Mechanistically, sestrin2 promoted the phosphorylation of the PI3K/AKT pathway, and inhibition of PI3K/AKT pathway abrogated the promoting role of sestrin2 in keratinocyte proliferation and migration. Therefore, sestrin2 plays a critical role in activation of the PI3K/AKT pathway to promote keratinocyte proliferation and migration, as well as re-epithelialization in the process of deep second-degree burn wound repair.
  • ||||||||||  MEN1611 / Menarini
    Trial completion date, Trial primary completion date, Metastases:  B-PRECISE-01: MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer (clinicaltrials.gov) -  May 24, 2023   
    P1,  N=62, Active, not recruiting, 
    Therefore, sestrin2 plays a critical role in activation of the PI3K/AKT pathway to promote keratinocyte proliferation and migration, as well as re-epithelialization in the process of deep second-degree burn wound repair. Trial completion date: Jul 2022 --> Dec 2023 | Trial primary completion date: Jul 2022 --> Dec 2023
  • ||||||||||  Journal:  Defining the role of mTOR pathway in the regulation of stem cells of glioblastoma. (Pubmed Central) -  May 22, 2023   
    Here we explored the role of the mTOR pathway in the regulation of stem cells of GBM by treating them with inhibitors of canonical PI3K/AKT/mTOR pathways such as rapamycin (mTORC1 inhibitor), PP242 (ATP binding mTORC1/2 inhibitor), LY294002 (PI3K inhibitor), and MAPK inhibitor, U0126...Treatment with novel small molecule inhibitors of mTORC1/2 demonstrated that Torin1 and Torin2 suppressed the proliferation of GBM CSC, while XL388 was less effective...Torin2 was able to eradicate tumor cells. In conclusion, Torin2 effectively targeted CSCs of GBM by halting self-renewal and inhibiting cell proliferation, underscoring the use of Torin2 in the treatment of GBM.
  • ||||||||||  lenalidomide / Generic mfg.
    Review, Journal:  Novel targeted drugs for follicular and marginal zone lymphoma: a comprehensive review. (Pubmed Central) -  May 19, 2023   
    We describe emerging data on approved and emerging novel therapies, such as targeted therapies (PI3K inhibitors, BTK inhibitors, EZH2 inhibitors), monoclonal antibodies and antibody-drug conjugates. Finally, we describe immune-directed approaches such as combinations with lenalidomide or the even more innovative bispecific T-cell engagers and chimeric antigen receptor T-cell therapy, which can achieve a high rate of durable responses with manageable toxicities, further obviating the need for chemotherapy.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Preclinical, Journal:  Synergistic actions of Alpelisib and Melatonin in breast cancer cell lines with PIK3CA gene mutation. (Pubmed Central) -  May 19, 2023   
    Targeting either RKIP or PTEN (alone or in combination with other therapies) may be sufficient to therapeutically inhibit tumor growth and reverse the tumor resistance to cytotoxic therapies. These results indicate that the combined use of Melatonin and Alpelisib may be more effective in inhibiting BC in women carrying the PIK3CA gene mutation than either treatment alone.
  • ||||||||||  Preclinical, Journal:  Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions. (Pubmed Central) -  May 17, 2023   
    Berberine also modulated PI3K/AKT pathway activity through up-regulating PTEN and down-regulating PI3K, AKT and p-AKT expression as well as suppressing its downstream targets, mTOR and p-mTOR at the protein level. Discussion/ These findings indicate that berberine inhibited growth, migration and invasion of these colon cancer cell lines via down-regulation of AQP 1, 3 and 5 expressions, up-regulating PTEN which inhibited the PI3K/AKT pathway at the gene and protein levels, and that AQP 1, 3 and 5 expression level can be used as prognostic biomarkers for colon cancer metastasis.
  • ||||||||||  Mekinist (trametinib) / Novartis, Torisel (temsirolimus) / Pfizer
    Journal:  Combination Treatment Targeting mTOR and MAPK Pathways Has Synergistic Activity in Multiple Myeloma. (Pubmed Central) -  May 16, 2023   
    Strikingly, the efficacy of temsirolimus was amplified by combining the treatment with the Mitogen-activated protein kinase kinase (MEK) inhibitor trametinib. Our findings provide a scientific rationale for the simultaneous inhibition of mTOR and MEK as a novel strategy for the treatment of MM.
  • ||||||||||  Firmagon (degarelix) / Astellas, Ferring, Aliqopa (copanlisib) / Bayer
    Journal:  Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer. (Pubmed Central) -  May 16, 2023   
    affects CLL B-cell numbers and T and myeloid cell pro-leukemia functions and support the use of duvelisib as a valuable approach for therapeutic interventions, including for patients refractory to BTKi. Immunometabolic strategies that reverse lactate and PD-1-mediated TAM immunosuppression, in combination with ADT, warrant further investigation in PTEN-deficient mCRPC patients.
  • ||||||||||  Treatment of ischemic heart failure through ultrasound-targeted microbubble destruction and it's mechanism (Science Box 1) -  May 13, 2023 - Abstract #ESC2023ESC_2913;    
    induced-chondrocytes by inhibiting PI3K/AKT/mTOR pathway and activating PINK1/Parkin and PINK1/Drp-1 pathway, thereby reducing the chondrocyte injury. The UTMD-mediated cavitation effect can rapidly improve the cardiac function of ischemic heart failure rats by activating PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.
  • ||||||||||  buparlisib (AN2025) / Novartis, Adlai Nortye
    BUPARLISIB A PROMISING THERAPEUTIC APPROACH IN CHRONIC MYELOID LEUKEMIA RESISTANT TO IMATINIB (Poster area) -  May 12, 2023 - Abstract #EHA2023EHA_2256;    
    Fractionated administration of BKM-120 was shown to be beneficial compared to a single administration, but only in resistant lines. The combination of BKM-120 and IMA induced a synergistic effect in all three cell lines but was more pronounced in the resistant models.
  • ||||||||||  Management of Diabetes in Cancer Patients (W-183C) -  May 11, 2023 - Abstract #ENDO2023ENDO_2765;    
    CGM use in cancer-related diabetes - a help or a hindrance? What is your practice?
  • ||||||||||  Piqray (alpelisib) / Novartis
    Journal:  PIK3CA copy number gain and inhibitors of the PI3K/AKT/mTOR pathway in triple-negative breast cancer. (Pubmed Central) -  May 11, 2023   
    Hence, we discuss the evidence presently available regarding a possible predictive value of PIK3CA amplification for response to targeted treatment strategies, suggesting that this molecular alteration might represent an intriguing biomarker in this sense. Considering that few of the currently active clinical trials assessing agents targeting the PI3K/AKT/mTOR pathway in TNBC select patients based on tumor molecular characterization, and none of these based on PIK3CA copy number status, we urge for the introduction of PIK3CA amplification as a criterion for patient selection in future clinical trials in this setting.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Expression and correlation of the Pi3k/Akt pathway and VEGF in oral submucous fibrosis. (Pubmed Central) -  May 9, 2023   
    VEGF expression correlated positively with the Pi3k/Ak activator, IGF-1. Due to the synergistic effect between Pi3k/Akt pathway and VEGF on OSF lesions and fibrosis process, targeted Pi3k/Akt pathway regulation can induce VEGF expression and improve ischemia, ultimately treating OSF.
  • ||||||||||  cisplatin / Generic mfg.
    Journal:  Targeting transient receptor potential canonical 1 reduces non?small cell lung cancer chemoresistance and stemness via inhibition of PI3K/AKT signaling. (Pubmed Central) -  May 8, 2023   
    Cisplatin-resistant A549 (A549/CDDP) and H460 (H460/CDDP) cells were first established and were then transfected with negative control small interfering (si)RNA (si-NC) or TRPC1 siRNA (si-TRPC1)...Finally, cell treatment with 740 Y-P reversed the effect of TRPC1 knockdown on PI3K/AKT signaling, chemoresistance, and cancer stemness in A549/CDDP and H460/CDDP cells (all P<0.05). In conclusion, the results of the current study suggested that targeting TRPC1 could attenuate cancer stemness and chemoresistance via suppression of PI3K/AKT signaling in NSCLC.
  • ||||||||||  Journal:  AS-605240 Blunts Osteoporosis by Inhibition of Bone Resorption. (Pubmed Central) -  May 8, 2023   
    Furthermore, AS enhances the differentiation of osteoblasts and inhibits bone loss due to OVX in vivo. AS inhibits osteoclast production and enhances osteoblast differentiation in mice, thus providing a new therapeutic approach for treating patients with osteoporosis.
  • ||||||||||  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) -  May 6, 2023   
    P1/2,  N=42, Recruiting, 
    Presented:ASH2022. Trial completion date: Oct 2027 --> Oct 2028 | Trial primary completion date: Apr 2025 --> Apr 2027
  • ||||||||||  Journal:  KLF2 inhibits colorectal cancer progression and metastasis by inducing ferroptosis via the PI3K/AKT signaling pathway. (Pubmed Central) -  May 6, 2023   
    Moreover, this KLF2-dependent ferroptosis in CRC cells was mediated by inhibiting the PI3K/AKT signaling pathway that resulted in the suppression of invasion, migration, and EMT of CRC cells. We report for the first time that KLF2 acts as a tumor suppressor in CRC by inducing ferroptosis via inhibiting the PI3K/AKT signaling pathway, thus providing a new direction for CRC prognosis assessment and targeted therapy.
  • ||||||||||  Istodax (romidepsin) / Astellas, BMS
    Synergistic effects of romidepsin with PI3K inhibitors in reducing the pool of HIV latently infected cells ex vivo () -  May 5, 2023 - Abstract #IASHIV2023IAS_HIV_1245;    
    We report for the first time that KLF2 acts as a tumor suppressor in CRC by inducing ferroptosis via inhibiting the PI3K/AKT signaling pathway, thus providing a new direction for CRC prognosis assessment and targeted therapy. Embargoes on oral abstracts and posters lift on Monday, 24 July 2023, at 09:00 Australian Eastern Standard Time (AEST).
  • ||||||||||  Piqray (alpelisib) / Novartis
    Journal, Stroma:  Tumor and stromal cell targeting with Nintedanib and Alpelisib overcomes intrinsic bladder cancer resistance. (Pubmed Central) -  May 5, 2023   
    Treatment with this combination is associated with cell cycle inhibition at the tumoral and stromal levels and potent non-tumor cell autonomous effects on ?-smooth muscle (SMA)-positive tumor infiltrating cells and tumor vasculature. The combination of Nintedanib with PI3K inhibitors not only reversed BC resistance to Nintedanib but also enhanced its anti-angiogenic effects.
  • ||||||||||  imatinib / Generic mfg.
    EFFECTIVENESS OF IMATINIB FOR MCTO NEPHROPATHY (Focussed Oral Room 2) -  May 4, 2023 - Abstract #ERAEDTA2023ERA_EDTA_1789;    
    Imatinib inhibits this pathway and suppresses TGF?. Imatinib may become a therapeutic agent for MCTO nephropathy.