Discover and read the best of Twitter Threads about #kras

Most recents (15)

There is a lot to consider in this first-line study of the #KRAS G12C inhibitor adagrasib plus pembrolizumab from #ESMOImmuno22. Some pleasant surprises in terms of safety. Definitely encouraging but need to see a bit more to be sold on this strategy. 🤔 #LCSM Image
We're looking for synergy with the two agents - more than an additive effect. Reason to believe there will be based on preclinical data showing the effect on T-cell infiltration from #KRAS inhibition. Similar to what has been shown with MEK inhibition. #ESMOImmuno22 Image
The first-line dataset includes the phase Ib KRYSTAL-1 and the phase II KRYSTAL-7. In KRYSTAL-1 (n=7), 4/7 had a response and all were durable (>9m). G3 TRAEs in 4 pts (lipase elevation, LFTs, muscular pain, pneumothorax). #ESMOImmuno22 ImageImage
Read 10 tweets
#KRAS alert! Over the past 4 years, a multi-disciplinary team from @hopkinskimmel @VUMC_Cancer @DanaFarber @MSKCancerCenter & @Amgen has been studying the distribution and co-mutations of KRAS, NRAS and HRAS mutant #cancers under the auspices of @AACR project #GENIE. Read the 🧵 Image
Our work is now published online at @CR_AACR and represents the largest study of RAS genomic architecture to date, leveraging #NGS data from >600,000 mutations and >66,000 tumors across 51 #cancer types.

Full text here
aacrjournals.org/cancerres/arti….
Our findings provide insights in the genomic architecture of RAS mutant cancers and may serve as a blueprint for mapping therapeutic vulnerabilities for mut RAS. Given the vast array of findings we have put together a shiny app for interactive #dataviz:
ras-hallmarks.jhmi.edu
Read 22 tweets
Oggi vi parlo di una bellissima scoperta di una proteina fondamentale per lo sviluppo del tumore al pancreas da uno studio tutto italiano pubblicato su Gastroenterology. Segue un thread da non perdere assolutamente. Let's go!
1/n 🧵#oncology #12febbraio
Il tumore al pancreas rimane a oggi uno dei tumori più letali e complessi da individuare: la scarsa percentuale di sopravvivenza è principalmente dovuta al fatto che la malattia, nelle sue fasi iniziali, non si manifesta con sintomi eclatanti. 2/n
Inoltre, la comprensione di tali fasi è ancora limitata, così come la conoscenza di marcatori molecolari per la diagnosi precoce. 3/n
Read 16 tweets
$NVS R&D day slides
novartis.com/sites/novartis…

$SAN $SNY Vaccine day slides from yesterday
Part 1
sanofi.com/-/media/Projec…
Part 2
sanofi.com/-/media/Projec…
$NVS featured multi-b$ products
$NVS Strategy to 2026
main approvals by mkt potential & current "strength of evidence"
earlier stage pipe in pharmaceuticals & oncology
Read 20 tweets
1/12 #TumorBoardTuesday
Thurs 10/12/21 Case🎀
@ShaalanBeg @CancerCommons present a case of #PancreaticCancer that challenges us to🤔about cell signaling & mol bio➡️better outcomes.

📚We captured as much of the chat as we could:
twitter.com/i/events/14479…
#PanCan #KRAS #OncTwitter
2/12 #TumorBoardTuesday
Thurs Case🎀

Take🏠messages:
We discussed #PancreaticCancer & specific #KRAS mut
✅All KRAS muts aren’t ≠
✅KRAS G12R➡️⬆️autophagy
✅Autophagy= tumor can♻️cell components ➡️resistance
✅MEKi + autophagy inhib= strat for G12R
✅Repeat NGS on prog is🗝️!
3/12
#TumorBoardTuesday
Thursday Case🎀

👉👉 Don’t forget to pick up 🆓 #CME credit by answering 3 quick ❓
Here is the post-test 🔗: bit.ly/3Bzgply

ALL CME 🔗: integrityce.com/tbt
Read 15 tweets
@curecc #ccfac2021 @noza512 @HopkinsMedicine presents on excitement about potential for peptide-based #vaccines as #immunotherapy for #cholangiocarcinoma ! Afterall, tumor recognition is king! And neoantigens critical... ImageImage
@curecc #ccfac2021 @noza512 Combo approach of #neoantigen vaccine + #immunotherapy can be highly effective! But #cholangiocarcinoma has lower #neoantigen burden c/w other tumor, higher T cell exhaustion ImageImage
@curecc #ccfac2021 @noza512 Trial soon to open...hope for opening for #cholangiocarcinoma in near future? Stay tuned! Image
Read 4 tweets
#ESMO20 Well done discussion by Dr. Colin Lindsay who wins for most random @Twitter handle - @mylovelypinata. Helpful reminder of the journey leading to direct #KRAS inhibitors and the achievements of medicinal chemistry leading to agents like AMG 510 and MRTX849. #LCSM ImageImageImage
#ESMO20 Sotorasib was safe and effective in #KRAS G12C NSCLC. Safety profile will allow for combinations: what are the right partners? Can we combine with IO? Do we need a phase III vs docetaxel? @mylovelypinata says absolutely, we do. And other KRAS mutations being targeted too! ImageImageImage
#ESMO20 Commenting on CHRYSALIS - amivantamab and lazertinib was safe and effective in osi-resistant and naive populations. Too early for cross trial comparisons but it seems as though IV drugs for #EGFR NSCLC are back. #LCSM #OncoAlert ImageImage
Read 3 tweets
#ESMO20 Much anticipated results from CodeBreaK100: AMG 510 (sotorasib) in #KRAS G12C #NSCLC by @DavidHongMD building on exciting data seen over the past two years for this huge unmet need. #LCSM @OncoAlert @myESMO Image
#ESMO20 KRAS G12C occurs in 13% of NSCLC, 3-5% CRC, and other tumors as well. Up until recently, considered "undruggable". Sotorasib is a highly selective KRAS G12C inhibitor that traps KRAS in its inactive GDP bound state. #LCSM @OncoAlert Image
#ESMO20 CodeBreak100 is a phase I escalation/expansion trial of sotorasib monotherapy in KRAS G12C tumors. Primary endpoint was safety. Escalation established preferred dose of 960mg qday. #LCSM @OncoAlert Image
Read 13 tweets
Bird’s-eye view 👁 on what to look out for @WCGIC #WorldGI2020.
Opening remarks on important data 📺 @myESMO - by Dr. Eric Van Cutsem @UZLeuven.
🟩Good to see more #PrecisionMedicine🧬
🟥#Immunotherapy #Immuno-#oncology
🟦TNT & other chemo strategies
@Annals_Oncology #OncoAlert
🆕#ctDNA #liquidbiopsies 🩸🧬
👀 👇🏾at the number of #clinicaltrials cropping up in this space‼️
🇦🇺DYNAMIC-II
🇦🇺DYNAMIC-III
🇺🇸COBRA @NRGonc
🇺🇸BESPOKE
🇺🇸@SU2C
🇯🇵 CIRCULATE
🌎COLUMBIA
🇮🇹🇪🇸PEGASYS
🇬🇧TRACC
🇩🇪CIRCULATE
🇫🇷crEATE
🇩🇰IMPROVE-IT
We have 2🇺🇸studies open. #CRCSM #WorldGI2020
#WORLDGI2020 This is 🆒 ☢️ 32-P EUS-guided implantation in #pancreascancer #PANCSM @myESMO @WCGIC @Annals_Oncology.

Still miles to go. OS median of 16 months pointing again to the systemic nature of disease. Need to piggyback these local approaches to better systemic. #OncoAlert
Read 55 tweets
What’s the difference between colon and lung? Not an easy question when it comes to #KRAS. Our work out today in @CD_AACR today describe a strategy to overcome resistance to KRAS G12C inhibition in CRC. @sloan_kettering @Albert0Bardelli @BardelliLab bit.ly/2ACWd7H👇👇👇
Molecular response to KRAS G12C inhibitors is different in CRC and NSCLC models. CRC models show quick MAPK pathway rebound
Receptor tyrosine kinases and EGFR dependency is stronger in CRC models
Read 5 tweets
#DCLUNG19 Daunting task of all non-EGFR/ALK drivers in #NSCLC handled easily by @alexdrilon - in #ROS1, note that not all ALK inhibitors are ROS1 inhibitors. Variation in CNS activity. Many active drugs to consider. #LCSM #LCAM ImageImageImage
#DCLUNG19 Highly active, CNS penetrant and well tolerated TKIs for #RET and #NTRK fusion positive cancers, outlined by expert @alexdrilon ImageImageImageImage
#DCLUNG19 Dabrafenib and trametinib active in #BRAF but be sure it’s V600E! Three drugs with breakthrough designation for #METex14. HER2 is a target but not copy number for #NSCLC, its mutations (usually ex20). #LCSM #LCAM ImageImageImageImage
Read 5 tweets
#WCLC19 Janna Minehart presenting rationale for CAR-T for #KRAS #NSCLC ImageImageImageImage
#WCLC19 Potential target is mesothelin, enriches in advanced disease and #KRAS #NSCLC - note the antigen heterogeneity though. Challenge in CAR-T strategies. Preclinically, dependent on antigen density. In trials though, responses also seen with low expression. #OncoAlert ImageImageImage
#WCLC19 But will need to overcome tumor mediated immunosuppression. Promising work. #OncoAlert ImageImage
Read 3 tweets
#WCLC19 Highly anticipated update on AMG510 in #KRAS #NSCLC by Ramaswamy Govindan does not disappoint. High RR (48%, 54% at 960mg) and DCR of 100%! No DLTs! Amazing early data in a huge area of need. #OncoAlert ImageImageImage
#WCLC19 AMG510 study design. Early look. Impressive PK profile at 960mg with low IC90 #OncoAlert ImageImage
#WCLC19 Swimmers plot for AMG510 shown here. Responses occur quickly. NOTE: not all of these responses are confirmed. Need to see how durable these are. Remember our experience with MEKi in #KRAS #NSCLC - RR nice but not durable (trametinib plot shown) #OncoAlert ImageImage
Read 3 tweets
Intriguing article in the June issue of @JTOonline by #JongWooLee and @DrRoyHerbstYale tackling the impact of #KRAS on the immune microenvironment in #NSCLC and the rationale for combining #MEK inhibition and anti-PD(L)1 therapy. #OncoAlert #LCSM

jto.org/article/S1556-…
Authors induced a p53/KRAS G12D mutant NSCLC. Compared to tumor free lungs, see a stark increase in CD45+ cells. Note, geographically localized to periphery/margin. Translational challenge: easy to miss with biopsies(aspirates not helpful). Image
Specifically, there’s a rise in neutrophils and MDSCs and a decrease in CD3+/CD8+ T cells in the tumor bearing lung (red bars below). Accompanied by rise in PDL1 expression (in tumor and MDSCs). Story: does this immune cell accumulation precede tumor development? Is it required? ImageImageImageImage
Read 10 tweets

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