Matt Waitkus

Our study identifies SMARCAL1 as a promising therapeutic target in ATRX-deficient ALT+ gliomas and supports future drug development of SMARCAL1 inhibitors for anti-cancer therapy.

Happy to share our latest study describing SMARCAL1 as a novel synthetic lethal vulnerability in ATRX-deficient gliomas. Just published in @NeuroOnc academic.oup.com/neuro-oncology…

@Dr_PViswanath @chadtough Thank you! Same to you!

@MattWaitkus @chadtough Congratulations!!

Excited to move this project forward and very grateful to @chadtough for supporting our work to develop new therapies for DMGs.

BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response dlvr.it/T6MwBg

@drmattmc @AngeloDipa_ @PDBrownOnc @StasLazarev INDIGO data indicate that a higher % of patients treated with upfront vorasidenib ultimately received a “subsequent anticancer therapy” vs patients who started on placebo. This doesn’t seem to support the interpretation that vora will delay RT/CT.

Respectfully I'm not sure INDIGO offers any credible data to support use of Vorasidenib over standard chemoRT: 2y LF 50% & ORR 11% with Vorasidenib (questionable design: Vorasidenib vs sugar pill for macroscopic disease) & dubious endpoints (image-guided PFS, rather than OS) 1/3

I feel like it has been a while since we talked about #CancerStemCells - excited to present a new review with @MarcoGalloLab just out in @NeuroOnc on #GBM CSCs led by @AnthonyrSloan @DJ_Silver_PhD #BTSM academic.oup.com/neuro-oncology…

With that background, we discuss our current understanding of how distinct TMMs (telomerase or ALT) may elicit specific vulnerabilities that can be targeted for glioma therapy.

We review the glioma subtype-specific genetic alterations that contribute to the induction of telomere maintenance mechanisms (TMMs) in pediatric and adult gliomas.

Our review on telomere maintenance mechanisms and associated therapeutic vulnerabilities is online today in Neuro-Oncology. academic.oup.com/neuro-oncology…

Led by talented postdoc @JoakinMori, our collaborative review in @JClinPath_BMJ with the Flynn Lab @BUMedicine on ALT in cancer @The_BMC

If you are seeking a postdoc position in the Neuro-oncology field, here is an exciting opportunity to join the Ashley Laboratory at Duke. Role is focused on the interplay between glioma epigenetics, DNA damage, and anti-tumor immunity. careers.duke.edu/job/Durham-POS…

@GeneCollector @PDBrownOnc the vast majority of placebo arm crossed over to vor at progression rather than proceeding to soc. see table S2. seems they counted crossover to vor from placebo as TTNI event, but not continued vor at progression on experimental arm.

@PDBrownOnc I might be missing something but why is the pfs curve so much worse than the ttni curve for the experimental arm. Did docs not treat at progression?

Putting Indigo Trial PFS benefit in context: · EORTC 22845 different era · RTOG9802 control arm ACTIVE treatment (RT as opposed to placebo) · RTOG9802 Chemo&RT PFS benefit ↑ if exclude IDHwildtype · After Vorasidenib resistance is Salvage Chemo&RT less effective?

@matthewherper pubs.acs.org/doi/10.1021/ac…

@matthewherper There is still confusion about this drug and its specificity. It is a pan-IDH enzyme inhibitor, with IC50 against the WT enzymes in the low nanomolar range. IDH1 is highly expressed in liver, potentially explaining in part the observed toxicities during prolonged trx.

This is going to be interesting to watch. A targeted cancer drug slowed the growth of a type of brain cancer dramatically. There is a but. The medicine, vorasidenib, also had some liver toxicity. #ASCO23 1/4 statnews.com/2023/06/04/gli…

Exciting work from Seetha and Ben on the countervailing effects of IDH1 mutations and ATRX deficiency on innate signaling pathways in LGGs. biorxiv.org/content/10.110…

I've been thinking a lot about this claim. It is complete bollocks. It reflects an arrogant, entitled mindset that has emerged in some "consortium genomics" participants. And while there is a lot of value in "big data" for biology, a naïve promotion of it is counterproductive. 1/

Out today @Nature. Our study describes how dysfunctional telomeres communicate with mitochondria to trigger a lethal interferon response. Looking fwd to feedback!   nature.com/articles/s4158…

New pre-print from the Bertuch lab shows that telomeric c-circles correlate with telomere length in telomerase+ cells. Provides further context and support for the idea that c-circles are not sufficient to classify ALT+ tumors/cells. biorxiv.org/content/10.110…

@JustinLathia Thank you!

@MattWaitkus Congrats Matt!

Happy to share that our study on the role of SMARCAL1 deficiency and alternative lengthening of telomeres is out today in Neuro-oncology academic.oup.com/neuro-oncology…