Up to 8 presentations, at least, specifically on paxalisib...or the use of PI3K drugs in the brain, at this forthcoming conference.
Almost too much information already here, to go into further detail. All of it good though and likely supportive for the drug. But that one I have highlighted in bold, sort of stands out. Radiation and PI3K, in the brain.
Kazia SHOULD already be in discussions with company - do a deal, don't wait any longer. (OR MANAGEMENT TO STAND ASIDE).
At the very bottom - more specific research, from Novocure, discussing how their radiation works with PI3K Inhibitors. This "Tumor Treating Fields" radiation technology is already approved for GBM. Novocure charge $20,000 per month for this treatment.
Tumor Treating Fields (TTFields) and a brain penetrant PI3K drug in GBM - would seemingly be critically urgent.
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NEXT WEEKS AGM of SNO
- Presentations
- Friday, November 18, 2022
- 10:20 AM – 10:30 AM ET
EXTH-12 - Preclinical and case study examination of the combination of the CLPP agonist ONC201 with the PI3K/AKT inhibitor paxalisib for the treatment of diffuse midline glioma.
Plenary Abstract Presenter: Matthew D. Dun, Ph.D (he/him/his) – Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
Preclinical Experimental Therapeutics
- ___________________________________________________________________________
- Saturday, November 19, 2022
- 11:55 AM – 12:00 PM ET
CTNI-27 - Multi-center, phase 2 study evaluating the pharmacokinetics, safety and preliminary efficacy of paxalisib in newly diagnosed adult patients with unmethylated glioblastoma (GBM)
Oral Abstract Presenter: Patrick Y. Wen, MD – Dana-Farber Cancer Institute
Clinical trials: Non-immunologic
_________________________________________________________________________POSTER PRESENTATIONS - PROFFERED ABSTRACTS| JUNE 15 2022
- Friday, November 18, 2022
- 10:20 AM – 10:30 AM ET
EXTH-12 - Preclinical and case study examination of the combination of the CLPP agonist ONC201 with the PI3K/AKT inhibitor paxalisib for the treatment of diffuse midline glioma.
Plenary Abstract Presenter: Matthew D. Dun, Ph.D (he/him/his) – Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
Preclinical Experimental Therapeutics
_______________________________________________________________________
- 7:30 PM – 9:30 PM ET
CSIG-19 - The PI3K/Akt/mTOR signaling cascade may contribute to sex differences in glioblastoma
Poster Presenter: Jasmin Sponagel, PhD (she/her/hers) – Washington University in St. Louis School of Medicine
Cell signaling and signaling pathways
Favorite
______________________________________________________________________- 7:30 PM – 9:30 PM ET
CSIG-41 - Sensitizing cancer cells to Tumor Treating Fields (TTFields) by inhibition of PI3K
Poster Presenter: Moshe Giladi, PhD, MBA – Novocure Ltd
Cell signaling and signaling pathways
__________________________________________________________________________
- 7:30 PM – 9:30 PM ET
DDDR-19 - Next-generation PI3K inhibitor for glioblastoma treatment
Poster Presenter: Kasen Hutchings – Virginia Tech Carilion School of Medicine
Drug discovery, drug resistance
___________________________________________________________________
- 7:30 PM – 9:30 PM ET
DDEL-08 - Novel Combination Therapy Using PI3Kinase Inhibition and Immune Based Therapy for the Treatment of Glioblastoma Multiforme
Poster Presenter: Ekokobe Fonkem, DO – (11) Barrow Neurological Institute
Drug delivery
_______________________________________________________________
- 7:30 PM – 9:30 PM ET
EXTH-17 - Combination of HDAC inhibitor and PI3K/mTOR inhibitor synergistically induces apoptosis in DIPG
Poster Presenter: HyukJean Kwon – Johns Hopkins School of Medicine
Preclinical Experimental Therapeutics
____________________________________________________________
- Sunday, November 20, 2022
- 12:05 PM – 12:10 PM ET
DDDR-10 - Inhibiting insulin signaling reverses resistance to PI3K-mTOR inhibitors in aggressive pediatric high-grade gliomas
Oral Abstract Presenter: Taylor A. Gatesman, B.S. – University of Pittsburgh School of Medicine
Drug discovery, drug resistance
______________________________________________________________
Abstract 2659: Inhibition of PI3K sensitized cancer cells to Tumor Treating Fields (TTFields)
Anat Klein-Goldberg;
Tali Voloshin;
Efrat Zemer-Tov;
Rom Paz;
Lilach Koren;
Kerem Wainer-Katsir;
Alexandra Volodin;
Bella Koltun;
Boris Brant;
Yiftah Barsheshet;
Tal Kan;
Adi Haber;
Moshe Giladi;
Uri Weinberg;
Yoram Palti
Author & Article Information
Cancer Res (2022) 82 (12_Supplement): 2659.
https://doi.org/10.1158/1538-7445.AM2022-2659
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Abstract
Introduction: Tumor Treating Fields (TTFields) are alternating electric fields, delivered noninvasively to the tumor site. TTFields therapy is currently approved for treatment of patients with newly diagnosed glioblastoma (GBM), recurrent GBM, or unresectable malignant pleural mesothelioma. Investigations are ongoing in additional tumor types, including non-small cell lung carcinoma (NSCLC), ovarian cancer, and hepatocellular carcinoma (HCC). Although TTFields have been demonstrated to extend life, most patients will eventually progress. The current research aimed to identify molecular mechanisms involved in reduced cancer cellular sensitivity to TTFields, and the potential of targeting these pathways to re-sensitize the cells to TTFields.
M
ethods: Continuous long-term application of TTFields (7 or 13 days, depending on the cell line) generated cancer cells with reduced sensitivity to TTFields. Luminex multiplex assay was used to detect changes in signaling pathways in ovarian A2780 and GBM U-87 MG cells, and relevant pathway markers were validated by Western blot. Further validation was performed by immunohistochemistry of tumor sections from N1S1 HCC tumor-bearing rats treated with sham or TTFields. The significance of the identified pathways in reducing cancer cell sensitivity to TTFields was evaluated through in vitro combination treatment with PI3K inhibitors, followed by cell count measurements. Finally, the concomitant application of TTFields and the PI3K inhibitor Alpelisib was evaluated in mice orthotopically implanted with MOSE-L firefly luciferase (FFL) ovarian cancer cells. Tumor volume was measured using the In Vivo Imaging System (IVIS) to detect the luciferin signal, before and after treatment.
Results: Cancer cell sensitivity to TTFields was reduced following continuous long-term application of TTFields. This was accompanied by activation of the PI3K/AKT/mTOR signaling pathway, with significant increases in the levels of phosphorylated AKT and RPS6 observed in cell cultures and in rat tumor sections following application of TTFields. Application of PI3K inhibitors re-sensitized the cells to TTFields in vitro. In vivo, concomitant application of TTFields with Alpelisib resulted in enhanced efficacy.
Conclusions: The current study demonstrated that reduced cancer cell sensitivity to long-term application of TTFields is mediated by activation of the PI3K/AKT/mTOR signaling pathway. Furthermore, PI3K inhibitors were shown to re-sensitize the cells to TTFields, providing a rationale for further examining the potential benefit of TTFields concomitant with PI3K inhibitors.
Citation Format: Anat Klein-Goldberg, Tali Voloshin, Efrat Zemer-Tov, Rom Paz, Lilach Koren, Kerem Wainer-Katsir, Alexandra Volodin, Bella Koltun, Boris Brant, Yiftah Barsheshet, Tal Kan, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Inhibition of PI3K sensitized cancer cells to Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2659.
Up to 8 presentations, at least, specifically on paxalisib...or...
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