Victor Velculescu at #AACR14 Presidential Symposium http://t.co/wmvmP6WKMK
10:13pm April 7th 2014 via Hootsuite
Velculescu: Opportunities through tissue and blood based genomic analyses: from tissue to liquid, static mutations to dynamic ones #AACR14
8:26pm April 7th 2014 via Hootsuite
Velculescu: 3rd - an approach for early detection. Detectable around the 1% level, want to get to 0.1%, dependent on seq costs #AACR14
8:24pm April 7th 2014 via Hootsuite
Velculescu: Case in neuroblastoma published in 2012 Nat Genet Sausen et al http://t.co/BgHjqbafNl #AACR14
8:23pm April 7th 2014 via Hootsuite
Velculescu: Plasma helpful when tumors may be difficult to access. Found ERBB2 amplification in 3/4 cases (unpubl data) #AACR14
8:22pm April 7th 2014 via Hootsuite
Velculescu: Approach is widely applicable - one would be monitoring after intervention; 2nd would be det. direct from plasma #AACR14
8:21pm April 7th 2014 via Hootsuite
Velculescu: Found rearrangements in both tumor and plasma ctDNA. Science paper looked at 600 samples; many 80-100%; others harder #AACR14
8:19pm April 7th 2014 via Hootsuite
Velculescu: Recently did this from plasma, Bettegowda et al Science 2014 Ref http://t.co/93Rt2bLkrq #AACR14
8:18pm April 7th 2014 via Hootsuite
Velculescu: Via PARE can use novel rearrangement as a biomarker and use PCR to measure across progression #AACR14
8:17pm April 7th 2014 via Hootsuite
Velculescu: Lays out PARE method. Leary et al 2010 Sci Trans Med paper http://t.co/36PLWsTr28 #AACR14
8:16pm April 7th 2014 via Hootsuite
Velculescu: Trends are more cancer exomes / targeted in early trials; cancer genome registry. #AACR14
8:15pm April 7th 2014 via Hootsuite
Velculescu: ~70% of cases have at least one gene mutated that action can be taken; but many limitations (i.e. limited evidence) #AACR14
8:14pm April 7th 2014 via Hootsuite
Velculescu: Pancreatic cancer - list of 14 genes that are potentially actionable. ~1/3 samples. Think about cancer as a genetic one #AACR14
8:12pm April 7th 2014 via Hootsuite
Velculescu:Translational work - targeting PALB2 (Mol Cancer 2011 paper) #AACR14
8:11pm April 7th 2014 via Hootsuite
Velculescu: Complexities of the cancer genome landscaped- mountains, across two tumors, only 3 genes overlap #AACR14
8:08pm April 7th 2014 via Hootsuite
Velculescu:Begins with chart of 'Seq analysis of the first 100 cancer genomes'. Emergence of cancer genetics / WG analyses #AACR14
8:07pm April 7th 2014 via Hootsuite
Next: Victor Velculescu, Johns Hopkins Kimmel CCC. "Personalized Genomic Analyses of Human Cancer" #AACR14
8:03pm April 7th 2014 via Hootsuite
AACR Presidential Symposium: "Precision Medicine: Next-Generation Sequencing" #AACR14
8:02pm April 7th 2014 via Hootsuite
Jain: Many other diseases could benefit from angiongenesis balancing. Hypothesized in 2001 Sci Am article http://t.co/fsJ0iJ0qUT #AACR14
7:22pm April 7th 2014 via Hootsuite
Jain: Can normalization of O2 improve immunotherapy? Yes. 2012 Huang et al PNAS 2012 http://t.co/oK1bMIR3TQ #AACR14
7:20pm April 7th 2014 via Hootsuite
@kennamshaw You got it - 5:30 in the Marriott lobby. See you soon!
7:17pm April 7th 2014 via Hootsuite in reply to
Jain: Treatment with cediranib, inc. tumor blood transfusion - survival benefit in two trials Batchelor PNAS http://t.co/icdgaeqZXf #AACR14
7:16pm April 7th 2014 via Hootsuite
.@kennamshaw I was planning to go - let me know where / when if you're up for going together. Dale
7:14pm April 7th 2014 via Hootsuite in reply to
Jain: Too much VEGF, too leaky. 2001 - use angiogenic drugs to repair. Idea: proper dosage to get O2 balance back. #AACR14
7:11pm April 7th 2014 via Hootsuite
Jain: Even if blood vessel is open, the blood flow / O2 level still insufficient (poorly perfused). Hose analogy: a leak? (VEGF) #AACR14
7:09pm April 7th 2014 via Hootsuite
Jain: Use of losartin to reduce stromal collagen. 2013 Nature Comm. paper Chauhan et al http://t.co/J1FO1Xm9l2 #AACR14
7:07pm April 7th 2014 via Hootsuite
Jain: Referred to this 2012 Cancer Cell paper Hingorani et al http://t.co/zqX7Ii2jr4 to target stroma enzymatically. #AACR14
7:06pm April 7th 2014 via Hootsuite
Jain: Depleting cancer cells, the blood vessels open up. But cancer cells only <5% of PDAC; rest is stroma. Destroy collagen? #AACR14
7:04pm April 7th 2014 via Hootsuite
Jain: Showed figures from this 2012 PNAS paper Stylianopoulos et al http://t.co/XONHr3Lf5h #AACR14
7:03pm April 7th 2014 via Hootsuite
Jain:Cut open a tumor - it opens up. The kidney tissue - no opening. Can calculate via math the force by the tumor #AACR14
6:59pm April 7th 2014 via Hootsuite
Jain: The garden hose analogy: what's constricting the input? What causes vessel constriction? Video of an orange (time-lapse) #AACR14
6:58pm April 7th 2014 via Hootsuite
Jain: 20y ago changed direction of the lab: looking at the net rate of O2 level in a tumor. 1988 Review http://t.co/GQC4ggn41G #AACR14
6:57pm April 7th 2014 via Hootsuite
Jain: 8 effects illustrated: genomic instab, angiogen, inflamm., anaerobic metab., EMT, induction of 'stem cell' phenotype... #AACR14
6:55pm April 7th 2014 via Hootsuite
Jain:Pressure pushes fluid out of the tumor, including drugs, causing edema. Hypoxia and low pH fuel many effects #AACR14
6:54pm April 7th 2014 via Hootsuite
Jain: Hetergeneous blood flow impedes drug delivery and creates hypoxia; raise interstitial fluid pressure too. #AACR14
6:53pm April 7th 2014 via Hootsuite
Jain: Nice figures shown from this 2010 Nature Methods Kim et al paper about tumor vasculature imaging http://t.co/kCT49eWM4n #AACR14
6:52pm April 7th 2014 via Hootsuite
Jain: Nice video from same 2009 paper - vessels become straighter, narrower. Using Doppler OFDI in murine mammary tumor #AACR14
6:50pm April 7th 2014 via Hootsuite
Jain: Microenv. shapes tumor biolology. 2009 Nature Medicine Vakoc et al PubMed: http://t.co/XvgpTP35GE #AACR14
6:49pm April 7th 2014 via Hootsuite
Jain: Each component of the microenv. is abnormal; if you can normalize / re-engineer it, you can improve outcomes. #AACR14
6:45pm April 7th 2014 via Hootsuite
8th Takamatusu Mem. Lecture: Rakesh Jain, Mass Gen Hosp.: Reengineering the tumor microenvironment to enhance cancer treatment #AACR14
6:34pm April 7th 2014 via Hootsuite
Carpten: Selected COLO 829 (CRL-1974) as it had data available on it already as a 'truth set' of 451 core mutations #AACR14
4:44pm April 7th 2014 via Hootsuite
Next: John Carpten, TGEN "Translation of cancer genomics knowledge to the clinic" #AACR14
4:32pm April 7th 2014 via Hootsuite
Chinnaiyan:Q:Handling heterogeneity? A:They see advanced cancers, heterogeneity isn't a large problem #AACR14
Chinnaiyan:Q:Include miRNA & epigenome? A:Needed to match available therapy. Can't link that data currently #AACR14
4:30pm April 7th 2014 via Hootsuite
Chinnaiyan: Distribution of categories: 57% Informative & actionable; 22 informative; 13 non-informative; 8% failed n=402 #AACR14
4:26pm April 7th 2014 via Hootsuite
Chinnaiyan: Reviewed 3 other vignettes - NAB2-STAT6 fusion; a rare FGFR kinas family fusion; and ESR1 mutations (all published) #AACR14
4:24pm April 7th 2014 via Hootsuite
Chinnaiyan: Found a KIF5B-RET fusion; highlighted this ref. Drilon et al Cancer Discov 2013 http://t.co/bf7NsyD4NF #AACR14
4:23pm April 7th 2014 via Hootsuite
Chinnaiyan:One example, adenocarcinoma, unk primary. Found 2 potentially sig CNV's, 3 germline variants; 41 somatic but no COSMIC #AACR14
4:20pm April 7th 2014 via Hootsuite
Chinnaiyan: Their precision med. tumor board - also genomics, clinical genetics, bioethics; try to classify into 5 groups #AACR14
4:12pm April 7th 2014 via Hootsuite
Chinnaiyan:Timeframe: Orig. 4w. Now ave is 6-8w 'not that acceptable'. Expect to get faster over time. #AACR14
4:10pm April 7th 2014 via Hootsuite
