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R&D dagen i sin helhet: https://vimeo.com/477021607
Veldig bra gjennomgang og veldig lærerikt kring AML, MDS (første 39 minuttene), Lung cancer (fra 39 min), hvorfor Bemcentinb burde testes i Mesothelioma sammen med Nivolumab/ipilimumab. (fra 51 min), SARS-CoV-2 (fra 1:08) og Fibrosis(Fra 1:38). Clinical development plan starter på 2:08.
Vel verdt tiden og veldig informativt kring indikasjonene og ikke bara BGBIO spesifikt.
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Flott, takk for den. Gikk glipp av fibrose-delen av konferansen.
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AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations
Received: 30 September 2020 / Accepted: 6 November 2020 / Published: 10 November 2020
https://www.mdpi.com/1422-0067/21/22/8419/htm (DOI)
In this review, we summarize the current knowledge of AXL functions and its implications in breast cancer progression.
Litt repetisjon på en tirsdag er vel sunt.
AXL Selective Inhibitors
BGB324 (Bemcentinib or R428) is the more selective ATP-competitive inhibitor of AXL (IC50 = 14 nM) and was the first to enter clinical trials to treat several cancer forms, such as TNBC tumors, metastatic melanoma and NSCLC. By blocking AXL autophosphorylation on tyrosine residue Y821, in vitro, it induces apoptosis, inhibits cancer cell invasion and reverts erlotinib resistance in TNBC cells; in vivo, BGB324 reduces cancer metastasis. In a recent preclinical study, BGB324 was tested in combination with auranofin, a gold phosphine derivative, initially used for the treatment of rheumatoid arthritis and also studied for the treatment of the other diseases, such as breast cancer. It is a thioredoxin reductase inhibitor and appears to induce apoptosis through PI3K pathway inhibition. The authors of this study have observed that in different breast cancer settings (MDA-MB231 and MCF7), the combination of BGB234 and auranofin reduced cell growth by inducing apoptosis, mediated by increased levels of Bcl-2-associated X-protein (BAX). Recently, BGB324 was implicated in a phase II clinical trial (NCT03184558) for TNBC and inflammatory breast cancers, in combination with pembrolizumab; however, the results have not yet been released
To date, BGB324 is the only AXL-specific inhibitor to be involved in clinical trials, although other highly selective molecules have been developed. Of these, however, there are only promising preclinical data which need to be extensively investigated. It is, therefore, clear that the process of development and the testing of new selective AXL inhibitors will require more time and more extensive studies, in the clinical field also. Analyzing the results described in this review, it is clear that AXL can be a potential marker in which to invest for breast cancer management and not only this, but there is still no solid and definitive evidence on its role in the clinical field. For this reason, it is auspicious to increase the study of selective inhibitors for AXL that can also be combined with other therapeutic regimens.
In recent years, cancer treatments have made important progress and the discovery of new target therapies has greatly improved the lives of patients and survival rates. However, despite the promising results obtained, oncology research has not solved two problems that are the causes of the most cancer deaths: (1) metastasis, with new characteristics as compared to the primary tumor; (2) drug resistance. For these reasons, it is essential to identify and study, always, new and alternative molecular targets to bypass these unfortunate conditions. Given its highly oncogenic characteristics and its involvement in many pro-tumorigenic processes, currently, AXL is considered a valid biomarker in several tumor contexts, primarily breast cancer. In this pathology, through uncontrolled activation of different downstream effectors, such as PI3K and MAPK, AXL regulates the malignant progression and migratory properties of breast cancer cells. Especially in TNBC tumors, AXL has been considered a key factor in the EMT process, promoting a mesenchymal and invasive phenotype. No less important is the role of AXL in several mechanisms of pharmacological resistance involved in the disease’s relapse, even in contexts previously responding to treatments. To date, several agents which inhibit the GAS6/AXL axis are being studied and have led to important results from both in vitro and in vivo experiments. Certainly, BGB324, due to its high selectivity for AXL, is the drug that has mainly produced significant results in terms of growth inhibition; in addition, it is the only specific AXL inhibitor to be involved in clinical trials for the treatment of several cancers. The development of new anti-AXL agents is always active, but even if preclinical studies have produced encouraging results in multiple tumor contexts, there is still a long way to go in clinical trials. Indeed, although different inhibitors of AXL have been developed, many of these are multi-target and are often implicated in clinical trials not for their inhibitory role on AXL. Therefore, the construction of new drugs, increasingly selective for this receptor, is always expected.
(Bemcentinib, also known as BGB324 or R428)
Edit:
La til «AXL Selective Inhibitors».
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BerGenBio presenterer fase-II bemcentinib kombinasjonsstudie i ikke-småcellet lungekreft (NSCLC) på den årlige SITC konferansen
BERGENBIO PRESENTS PHASE II BEMCENTINIB COMBINATION STUDY IN NSCLC AT ANNUAL SITC MEETING
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Var det noe særlig nytt her da? Dette er vel mer eller mindre det samme meldt i sommer…?
Var vel cohort A som ble meldt i sommer.
Den også. De oppdaterte cohort a mOS til 17,3 måneder (and still maturing), så jeg tror det kommer mer her…
De nevnte tallene i cohort b var akkurate like i sommer. Da på 12/16 pasienter.
Trodde også vi kunne vente noe fra cohort c, men det kommer kanskje i slutten av Januar…
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Ikke at det trenger å bety så mye, men pent at SITC setter Bergenbio øverst av highlights på sin blog.
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Synes vi er i overkant beskjedne her på vegne av BergenBio 
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For få bergensere i aksjonærmassen 
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Q3 i morgen. Har vi noen forventninger, eller ei?
Det må vel være oppdatering på Covid-studiene.
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covidstudie har vi vel fått vite at sliter med rekrutteringen, ref R&D day eller hva de kalte det.
Kan hende at vi får dummet ned noen av resultatene fra de kliniske studiene sånn at hvermannsen kan forstå? Men kliniske nyheter får vi neppe.
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Hvis alt klaffer planlegges det å vaksinere etpar titusener i Norge i 2021.Bergen bio sin medisin hvis den virker vil det være behov for i lang tid fremover og ikke minst ved lungefibrose.
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Med de 2 millioner dosene Norge har bestilt av vaksiner, så er det vel ca en million som blir vaksinert forsto jeg, ikke 20.000-ish?
Men det vil jo likevel være behov for medisiner som f.eks Bbio sin, hvis den viser effekt.
Har hørt 21000 tusen, og resten kommer senere.Vet ikke hva myndighetene sitter på her
"– Vi ser veldig lovende resultater fra BioNTechs vaksine. Og så venter vi på resultater fra to andre vaksiner nå de neste ukene.
Det sier John-Arne Røttingen til TV 2. Han er administrerende direktør i ForskningsrådetNorge kan få to millioner doser av vaksinen når den er klar.
– Det tar tid å lage så mange doser vaksine som verden trenger. Derfor kan det ta noe tid før vi gradvis kan begynne å vaksinere i Norge, sier Røttingen. Han mener dette kan skje i mars eller april."
Jeg sitter uansett stille i Bergen bio. De har en veldig spennende pipeline i kreft, så coronovirus behandling tar jeg kun som en eventuell bonus.
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