RT @MartinEglitis: You think your fancy mechanism is the way your drug is working, but it's not. Which is fine for onc drugs, where cell de…
You think your fancy mechanism is the way your drug is working, but it's not. Which is fine for onc drugs, where cell death is the goal. But a worry for other indications where you may actually want to preserve/restore cells! (h/t @IlyaYasny @LacertaBio h
@hiphopchopchop @BGatesIsaPyscho A study on cancer drugs found that 97 % of the tested anti-cancer drugs killed tumors through off-target effects such as inhibiting CK11 that a lot of cancers utilize. The neoantigent-based tech is described as targeting. h
It's a fascinating and very creative study but limited by the physiologic relevance of its competition assay.
RT @SashaGusevPosts: Or that a large fraction of cancer drugs with decades of preclinical evidence and in clinical trials actually kill tum…
Or that a large fraction of cancer drugs with decades of preclinical evidence and in clinical trials actually kill tumor cells through unknown off-target effects and not their hypothesized mechanism [https://t.co/vqS7jIv4hl]. https://t.co/WBFQtUSSyh
@RuxandraTeslo also off-target effects are much more common than we anticipated: https://t.co/vqS7jIv4hl
Drugs may not do what we think they do: Lin et al. discovered that a drug candidate in clinical development was effective at killing cancer cells even when its target protein was knocked out https://t.co/EN115MshzR
#オフターゲット毒性 は #臨床試験 における #抗がん剤 の一般的な #作用機序 である 2019 @CSHL 〜 要約:#腫瘍学 で #臨床試験 された薬剤の 97% は #業界団体 @US_FDA から承認されない。〜 https://t.co/z7Cnte7Adv
RT @JSheltzer: In other words, the cytotoxic effects of ricolinostat are entirely independent of HDAC6 inhibition. It still kills cells tha…
RT @JSheltzer: In other words, the cytotoxic effects of ricolinostat are entirely independent of HDAC6 inhibition. It still kills cells tha…
RT @JSheltzer: In other words, the cytotoxic effects of ricolinostat are entirely independent of HDAC6 inhibition. It still kills cells tha…
RT @JSheltzer: In other words, the cytotoxic effects of ricolinostat are entirely independent of HDAC6 inhibition. It still kills cells tha…
In other words, the cytotoxic effects of ricolinostat are entirely independent of HDAC6 inhibition. It still kills cells that totally lack HDAC6 expression. Source: https://t.co/VRUg85VlUE
https://t.co/O1EDhrdmEU A 2019 paper, but I only came across it recently. An astonishing number of cancer drugs primarily operate through off-target toxicity. Shows there is so much potential in optimizing screening approaches.
RT @JSheltzer: We saw this in a previous paper from our lab - https://t.co/VRUg85VlUE. We generated 12 single-cell derived clones from MDA…
We saw this in a previous paper from our lab - https://t.co/VRUg85VlUE. We generated 12 single-cell derived clones from MDA-MB-231 transduced with gRNAs targeting non-coding loci, and we found huge variability in the proliferative capacity of these “contr
Ever wonder how many cancer drugs (or any drugs, really) actually make it to market? Well, the *OLD* way gives us as much as a 97% fail rate. Finding out if they work earlier would save so much money. https://t.co/sYailWOIEQ Do CRISPR. Find out faster.
@CellDeathLab in https://t.co/VRUg85DKw4, we knocked out MAPK14 in 32 different cancer cell lines, including MiaPaca2, HT29, K562, etc., that score high for MAPK14 dependency in DepMap. No loss of fitness! I think that this is a (rare) instance of inaccura
@mbsoellner 1) No published kinomescan, I bet it would parallel the individual kinase assays we did and show stronger binding to p38a vs. EGFR. 2) I'm not sure any lines are dependent on MAPK14. See Fig S2 in https://t.co/VRUg85VTKc, which includes HT29.
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
#OTS964 10x more selectivity than the state-of-the-art #CDK11 inhibitors. (See Lin et al. who reported OTS964 (https://t.co/NPSj7jKo3O) targets CDK11 rather than TOPK; indicates the value of validating targets CRISPR KO + #chemogenomic sets) cc: @EUbOPEN
A dose of humility in drug development "Drugs may not do what we think they do" Great analysis https://t.co/NTyU5s5CcZ
My lab discovered that for many different clinical cancer drugs, we could delete that drug’s putative target, without affecting drug sensitivity! This means that the drug is functioning through some other mechanism. https://t.co/VRUg85VTKc
In 2019, my lab used CRISPR to study two clinical HDAC6 inhibitors, citarinostat and ricolinostat. We generated HDAC6-knockout clones, and we demonstrated that their anti-cancer activity was entirely independent of HDAC6 expression (!!). https://t.co/RPsw
@KRHornberger @varma_ashwin97 @JSheltzer Should probably link the paper… https://t.co/nvp8yMBGSk
About a week ago I read "Every gene can (and possibly will) be associated with cancer." Perhaps false positives from RNAi off-targeting could have played a part in inflating the number of cancer-related genes (79/n) https://t.co/hPGninhLdg
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
@deniswirtz @arjunrajlab Several drug validations as well. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/RKCdwdcbT5
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
@MedCrisis There are a bunch of cancer drugs that work and we have no idea why. In this study they looked at 10 anticancer agents and studied their proposed mechanism of action. Turned out that all 10 agents worked even without its intended drug target.
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @cancerassassin1: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/ncw2ZzStBB
RT @cancerassassin1: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/ncw2ZzStBB
RT @cancerassassin1: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/ncw2ZzStBB
RT @cancerassassin1: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/ncw2ZzStBB
Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/ncw2ZzStBB
@andy_utoronto @JSheltzer has done interesting work on this issue. As you suggest, many FDA-approved drugs have very different mechanisms-of-action than they say on the tin. https://t.co/pIY3EDwiug
Wow
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
Great talk by @JSheltzer at WCM this morning on this important work. Makes me want to quintuple my number of controls and never touch RNAi again 😬
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @Frank_S_David: @thebyrdlab @statesdj Sounds about right. Here’s another recent take on the topic: https://t.co/5h6xdEtO2u
@thebyrdlab @statesdj Sounds about right. Here’s another recent take on the topic: https://t.co/5h6xdEtO2u
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials | Science Translational Medicine https://t.co/sbhJkLjkGj
RT @RBoggess14: Here's a very cool paper given to me last year by my PI, Dr. Tamae. Often, a result is desired but the difficulties associa…
RT @RBoggess14: Here's a very cool paper given to me last year by my PI, Dr. Tamae. Often, a result is desired but the difficulties associa…
Here's a very cool paper given to me last year by my PI, Dr. Tamae. Often, a result is desired but the difficulties associated with success is overlooked. This paper shows one of the many challenges associated with designing a new therapeutic. #2020CSUICM
RT @dmeyzie18: @VPrasadMDMPH Was late to the party only discovering his work with this beauty: https://t.co/C0BWc4PpRs He’s a spectacular…
RT @dmeyzie18: @VPrasadMDMPH Was late to the party only discovering his work with this beauty: https://t.co/C0BWc4PpRs He’s a spectacular…
RT @dmeyzie18: @VPrasadMDMPH Was late to the party only discovering his work with this beauty: https://t.co/C0BWc4PpRs He’s a spectacular…
RT @dmeyzie18: @VPrasadMDMPH Was late to the party only discovering his work with this beauty: https://t.co/C0BWc4PpRs He’s a spectacular…
... know if the level of activity sufficient to cure a mouse will be enough for a human. + Fascinating initial discussion on @JSheltzer work on drugs that don't hit their putative target. This is seen with crispr knock outs 2/2 https://t.co/2EpG2dpeY8
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
@LastBehaviorist @Ersant0s @PBaboins @kareem_carr @EricRWeinstein @ConceptualJames These sorts of issues are constantly lurking in many fields. Frankly, I think it is an illusion that the merely having some experimental control eliminates the need to think
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/eLiHU1aghN via @ScienceMagazine @JSheltzer
@Prof_Livengood But, RNAi was not an ideal experimental manipulation at all, it had lots of off-target effects that used to be ignored. And more recent work shows that people got the mechanisms wrong https://t.co/un3q2vUcu1
Ahora se está revirtiendo esa mala tendencia, y la validación genética de potenciales tratamientos es uno de tres motivos citados aquí https://t.co/Q8XpQ21LXU (no todo es por bases de datos de diversidad genética, otras cosas nuevas también ayudan, veáse
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
@UrnovFyodor @berkeleyMCB I think the work by @JSheltzer is a striking example. https://t.co/4TuEeTWBxU
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
@stuartbuck1 @A_Schwa @Jabaluck @rabois In cancer, we often don't understand mechanisms well. Hidden gene(s) on or off could be correlated w/ S failure and also G success. If we did understand them well I would not recommend the aforementioned design. htt
@lakens Surely one of my favorite ones in 2019. Read it on the train to my holidays and couldn't stop thinking about it until I ultimately arrived in Italy. ;-) @JSheltzer https://t.co/6p99gRpNs6
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
RT @joachimgoedhart: The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly…
The inspiration for my recent blog @MyBioTechniques was a mind-blowing paper by @JSheltzer and colleagues - I highly recommend reading it (it is also great teaching material in the domain of biomedical sciences). blog: https://t.co/8BNj1pe2g0 paper: http
"Stay on target!" Karen Anderson @YaleMed recommends this article @MGHCancerCenter that discovers some #cancer drugs work through off-target mechanisms rather than the intended one https://t.co/iUFI6dnVC4 https://t.co/tunar9qzy0
RT @SSP_PEI: Thought-provoking read: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https:/…
RT @SSP_PEI: Thought-provoking read: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https:/…
Thought-provoking read: Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials https://t.co/TL2fO75KEd
@ScottGottliebMD We may need to rethink how "well understood" the mechanism of action of drugs are. Ex: https://t.co/wDX1HxFNek
Worthy read! https://t.co/caFmffWIoC
RT @JSheltzer: Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in c…
RT @raqbio: OTSの開発したMELK阻害剤OTS167及びTOPK阻害剤OTS964(514)が、実際はoff-targetに作用してがん細胞に影響しているのではないか?ということに一部触れている論文 https://t.co/HodC9S9pma
RT @DoctorBou: “97% percent of drug-indication pairs that are tested in clinical trials in oncology never advance to receive U.S. FDA appro…
OTSの開発したMELK阻害剤OTS167及びTOPK阻害剤OTS964(514)が、実際はoff-targetに作用してがん細胞に影響しているのではないか?ということに一部触れている論文 https://t.co/HodC9S9pma
RT @CancerConnector: @EricTopol @kaznatcheev As for missing ‘shake-ups’ I’d add @JSheltzer gorgeous work showing when we use targeted thera…
RT @EricTopol: @ellie_kincaid @ivanoransky @Medscape Adding 3 2019 papers that challenged conventional wisdom: 1. Off-target toxicity of #c…