Bar-Sagi #AACR23 And 2) Identification of local and systemic nodes of immune modulation: a necessity to improve therapeutic success?
5:41pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 IL15 agonists could control tumor immunity; trying a Ph Ib trial for pancreatic cancer. 2 take hom… https://t.co/7WszUXcs9o
5:40pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 Of course reducing risk of cardiac disease. Exercising mice - IL15 driving activation of cytotoxic… https://t.co/FiGpXS6Nk9
5:39pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 The last layer - the macrosystem, the organismal environment. There are multiple aspects of physio… https://t.co/ulcqZSS7j4
5:36pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 Onto the organ-level: PDAC metastatic organotropism. Will not tweet about content ("do not post" s… https://t.co/qV9zoM8pOj
5:30pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 Onto a second example- microenvironment-mediated reprogramming of the immune phenotype from TLR4 v… https://t.co/pD5opVK2dm
5:25pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 Have seen mutant KRAS-dependent modulation of the immune environment. Showed up-regulation of GM-CSF via MAPK and PI3K.
5:17pm April 15th 2023 via Twitter Web App
Dafna Bar-Sagi (NYU Langone Health, NY) #AACR23 Disruption of immune homeostasis circuits in mutant Ras tumors: Who… https://t.co/9oPTnObeWM
5:15pm April 15th 2023 via Twitter Web App
Janne #AACR23 A selective G12D inhibitor called MRTX1133, clinical trials in 2023. Now onto combinations of Ras inh… https://t.co/wtHjgIadBB
5:08pm April 15th 2023 via Twitter Web App
Janne #AACR23 Revolution medicines slide RMC-6235, much better 44% to 61% ORR in CRC, PDAC. Early pre-clinical data… https://t.co/cdZQ5lJCrP
5:03pm April 15th 2023 via Twitter Web App
Janne #AACR23 How to improve G12C inhibitors? Shows a huge list - perhaps 12 - in early Ph I / II trials. JDQ443, G… https://t.co/I7dVklb28v
4:59pm April 15th 2023 via Twitter Web App
Janne #AACR23 Cp sotorasib and docetaxel in CRC data shown. Cp of resistance mechanisms. In CRC have seen multiple… https://t.co/hbBAuNi9gt
4:58pm April 15th 2023 via Twitter Web App
Janne #AACR23 metastatic pancreatic cancers - 6.6 mos PFS. Other GI cancers - median PFS 7.85mos. CRC - PFS 5.6 and… https://t.co/CxMC3DUtpP
4:55pm April 15th 2023 via Twitter Web App
Janne #AACR23 Shows Ph I / II trials, Adagrasib and Sotorasib. Shows PFS of 7 mos for both. Q: can it cross the blo… https://t.co/8f4IebMChz
4:53pm April 15th 2023 via Twitter Web App
Janne #AACR23 Poor therapeutic index and lack of efficiency in drugs targeting KRAS signalling. Toxicity is a major… https://t.co/6zZ6H0kXav
4:50pm April 15th 2023 via Twitter Web App
Pasi Janne (Dana-Farber Cancer Inst MA) #AACR23 Progress in the treatment of KRAS mutant tumors.
4:47pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Switch 1 can be in one of two states. Credits Frederick National Lab and Bridge Bio, along with LLNL.
4:46pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Now targeting KRAS in the GTP-bound state. G12D, and G12V. Can show binding of H95 ('switch two p… https://t.co/FpLesfOyzJ
4:44pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Blocking PI3 kinase activity is optimistic on development. Onward to direct binding to KRAS 2012,… https://t.co/O24r8MUsth
4:41pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Targeting kinases in 1995 was still just an idea. Idea 2: restore mutant RAS GTPase activity? 199… https://t.co/ffMC4jLGzE
4:38pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Tipifarnib tested in HRAS mutant cancers. 1992: how to target RAS directly? resistant to GAP, ind… https://t.co/qsFF8AW48p
4:33pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Top-down MS identifies multiple RAS isoforms in cancer cells. Abundant proteoforms w/in a Panc1 c… https://t.co/AmUEYEbrEC
4:31pm April 15th 2023 via Twitter Web App
McCormick #AACR23 1984 RAS processing is essential - palmitoylated, farnelsol modified, C-terminus required.
4:30pm April 15th 2023 via Twitter Web App
McCormick #AACR23 1985, he was able to specifically inactivate KRAS oncoprotein, right about the time PCR was inven… https://t.co/afG4Z4xyGX
4:27pm April 15th 2023 via Twitter Web App
McCormick #AACR23 1982 re-discovery of HRAS in human tumor DNA, HRAS G12V, KRAS G12R, NRAS Q61K. NIH 3T3 focus form… https://t.co/cV6iiaCeC6
4:26pm April 15th 2023 via Twitter Web App
McCormick #AACR23 '67 discover KRAS (v-Ki-MuSV), G12R, A59T is v-Ha-MuSV; G12S, A59T is v-Ki-MuSV. Mice has strong… https://t.co/i4FUFQrBTJ
4:24pm April 15th 2023 via Twitter Web App
McCormick #AACR23 Has been working on targeting Ras since 1982. Started with discovery in 1964 of moloney leukemoge… https://t.co/nyAeiqkniE
4:21pm April 15th 2023 via Twitter Web App
Bar-Sagi #AACR23 "Let me tell you, it did not happen overnight." "...and perhaps this session will inspire some her… https://t.co/xXDNgOKyo2
4:19pm April 15th 2023 via Twitter Web App
Plenary session Beating KRAS: a 30-year Overnight Sensation #AACR23 Opening: Dafna Bar-Sagi (NYU Langone Health) St… https://t.co/MoioaRG84X
4:16pm April 15th 2023 via Twitter Web App
Q: What about the costs of a biomarker-included clinical trial? A: Yap #AACR23 Why do procedures cost so much? Who… https://t.co/P4dtUZTLrM
3:50pm April 15th 2023 via Twitter Web App
London #AACR23 Storage and handling and instrument drift. It's common to have systematic difference in subject sele… https://t.co/qW9HbuVXRo
3:36pm April 15th 2023 via Twitter Web App
London #AACR23 Should be unambigous - and the NCI does not have minimum standards... Avoiding bias: less 'haphazard… https://t.co/4nqtcshq79
3:35pm April 15th 2023 via Twitter Web App
Wendy London (Boston Children's Hosp, MA) Statistical and practical guidance for biomarker studies #AACR23
3:24pm April 15th 2023 via Twitter Web App
Yap #AACR23 The goal is to do away with 'painful biopsies' and have cfDNA. Yap et al JCO 2013 was 10 years ago. https://t.co/Ycbx6GJHJX
Yap #AACR23 Using ddPCR shows ctDNA declines in those who respond. Idea - select pt, treat and use cfDNA to monitor disease, and switch Rx.
3:20pm April 15th 2023 via Twitter Web App
Yap #AACR23 With AKT "impressive PK-PD profile but limited anti-tumor responses; is it the target / pathway?" Then… https://t.co/A7MFfN1gnI
3:19pm April 15th 2023 via Twitter Web App
Yap #AACR23 Pivots to AKT inhibitor, going back to 2003 at Inst Cancer Res (London); he did first-in-human trial ch… https://t.co/dRA3nZpbux
3:14pm April 15th 2023 via Twitter Web App
Yap #AACR23 Shows nice slide of what is needed before a trial, and during a trial. Before: biomarker dev in paralle… https://t.co/Q3LfojCDOg
3:07pm April 15th 2023 via Twitter Web App
Yap #AACR23 The whole development has to be "a re-iterative, parallel process", as you want PD (and PK), 'how much'… https://t.co/K37WmIWeVp
3:06pm April 15th 2023 via Twitter Web App
Yap #AACR23 Focus on PD and protective biomarkers. Why to include biomarkers? "I want to make my trial 'cool'... it… https://t.co/Dn3fcWjQDv
3:00pm April 15th 2023 via Twitter Web App
Timothy Yap (UT MD Anderson Houston TX) #AACR23 Incorporation of proof-of-mechanism pharmacodynamic biomarkers and… https://t.co/K1cRKWyqwN
2:57pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Take home message - one is 'use samples efficiently' "(multiplexing when possible)" TAKE NOTE OF THIS
2:56pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Has a TNBC study, PARPi alone or with anti-PD-L1. Biomarker intensive, three biopsy and blood. Oft… https://t.co/zGZEqohnjK
2:54pm April 15th 2023 via Twitter Web App
Schalper #AACR23 shows a list of 10 selection and prioritization items - objectives, sample type, context, statisti… https://t.co/U7WGfNb8Hx
2:51pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Shows data from 2015 how subset of TILs assoc with inc survival.
2:49pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Now onto mIHC - with four dyes (DAPI/CK etc.) CD4/CD8 co-stained slide shown. Showed reprod across… https://t.co/3hwpML9ePH
Schalper #AACR23 DNA/RNA alternation using Oncomine v3 (used with NCI-MATCH). 161 genes: orthog validation for spec… https://t.co/ebZX6Ua7ZT
2:46pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Biomarker validation - example of validation strategy; need to show 1) specificity (including +/-… https://t.co/q8HPVncowV
2:44pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Mok et al 2008 IPASS progression-free survival in EGFR-mutation+ versus - patients. Working / not… https://t.co/LhFIelPhpl
2:41pm April 15th 2023 via Twitter Web App
Schalper #AACR23 Impact - reveal biological determinants of pt, disease and treatment. -evaluate effect and timin… https://t.co/FViZ79smuU
2:38pm April 15th 2023 via Twitter Web App
