Remember this, from world leading hospital Memorial Sloan Kettering.
And at very bottom - More most interesting recent research from Germany - using a near 20 year PI3K drug and achieving success, with this "old" PI3K drug , standard chemo and especially radiation in head and neck cancers.
This German research (refer earlier thread postings) - backs up what we heard from MSK in August last year. The 20 year drug verse paxalisib .....how might that go.
You might even be tempted to say now.... that PI3K drugs eg Paxalisib - significantly do in fact, enhance radiation treatment in cancer. Very compelling stuff - its not a Kazia study, this abstract comes from Memorial Sloan - how the hell do you value this drug ?
--------------------------------------------------- Published 5th August 2022
MMAP-05 PHASE I STUDY OF CONCURRENT PAXALISIB AND RADIATION THERAPY IN PATIENTS WITH SOLID TUMOR BRAIN METASTASES OR LEPTOMENINGEAL METASTASES HARBORING PI3K PATHWAY MUTATIONS: RESULTS FROM THE DOSE-ESCALATION COHORT
When combined with cranial RT, the paxalisib MTD was established at 45mg/day. We also observed robust response with all evaluable patients experiencing partial or complete response per RANO-BM within 3 months of protocol therapy.
From Wikipedia, the free encyclopedia RE this old PI3K drug in the bottom listed research.
Dactolisib (codenamed NVP-BEZ235 and BEZ-235, also known as RTB101) is an imidazoquinoline derivative acting as a PI3K inhibitor.[1] It also inhibits mTOR.[2] It is being investigated as a possible cancer treatment.[3]It was the first PI3K inhibitor to enter clinical trials, in 2006.[5
Dual pi3k/mtor inhibitor nvp-bez235 leads to a synergistic enhancement of cisplatin and radiation in both hpv-negative and -positive hnscc cell lines
13/04/2023 HIGHLIGHTS
HIGHLIGHTS
who: Florentine S. B. Subtil et al. from the Department of Radiotherapy and Radiooncology, Philipps-University, Marburg, Germany have published the research: Dual PI3K/mTOR Inhibitor NVP-BEZ235 Leads to a Synergistic Enhancement of Cisplatin and Radiation in Both HPV-Negative and -Positive HNSCC Cell Lines, in the Journal: Cancers 2022, 14, x. of 21/06/2022
what:The aim of this study was to test whether BEZ235, which is an effective dual inhibitor of the PI3K/mTOR signaling pathway, can be used to enhance the effect of cisplatin alone, but especially when combined with radiation.
SUMMARY
In contrast, when using viability tests for both radiation as well as cisplatin, a lower degree of sensitivity was measured for HPV pos. cells when compared to HPV neg. cell lines. Both entities show similar degrees of expression of RAD51, but for HPV pos. cells, the KD of RAD51 was found to have no effect on cisplatin sensitivity, while a clear increase was observed for HPV neg. cells. In line with this, for HeLa cells, KD of RAD51 was found to result in an increased degree of cisplatin sensitivity, and for NSCLC cells, impaired RAD51 foci formation was associated with enhanced cisplatin sensitivity. When HR was also depressed in HPV neg. cells via KD of RAD51, a similar degree of enhancement of cisplatin by BEZ235 was obtained, as for HPV pos. cells. As a consequence, more cell killing is induced in the HR deficient HPV pos. cell lines.
For HNSCC cells, only additive effects were generally seen when cisplatin was combined with radiation, and for some cells, even a decrease in radiosensitivity was measured. The enhanced cell killing effect of the combined treatment with cisplatin and radiation when using a pretreatment with BEZ235 was seen for both HPV neg. and pos. cells, with a slightly stronger effect for the latter. Some of the unrepaired cisplatin-radiation adducts will also interfere with replication, therefore causing more cell killing in HR-deficient HPV pos. cells. This explains why the enhancement of the combined treatment with radiation and cisplatin by BEZ235 was stronger for HPV pos. cells. @@
KZA Price at posting:
19.0¢ Sentiment: Buy Disclosure: Held
