Swanton: Now able to predict and detect neoantigen reactive T-cells (NAR-T) in NSCLC, a tetramer analysis #AACR16
9:43am April 19th 2016 via Hootsuite
Swanton: Analysis of exomes - clonal neoantigens in PD1 resp. Subclonal neoantigens in PD1 prog disease #AACR16
9:41am April 19th 2016 via Hootsuite
Swanton: Onto neoantigens - MSKCC, looked at PD1 responders at 6mos, and PD1 progressive disease #AACR16
9:40am April 19th 2016 via Hootsuite
Swanton: Exposed to asbestos, BPA, polycyclic hydrocarbons. Also worked in road construction. Long list of hazards #AACR16
Swanton: One outlier - never smoker, 1300 coding mut's in trunk; very homogeneous tumor. Occupation: petrochemical worker #AACR16
9:39am April 19th 2016 via Hootsuite
Swanton: Long-smokers have a trunk much longer than never-smokers. 5-8x coding mut's. Case of 600 coding mut's in trunk, 100 branch #AACR16
9:38am April 19th 2016 via Hootsuite
Swanton: Today we target early founder events; but resistance inevitable. Want to target multiple turnk/clonal events in every cell #AACR16
9:36am April 19th 2016 via Hootsuite
Swanton: Median 0.3% of clonal mutations. 0.1% subclonal muts. Stage 1A highest failure rate 'results are certainly promising' #AACR16
Swanton: 2-24 pre-surgery, collect cfDNA, select 15-20 NSVs/patient, total 884 assay from 50 pts, detects 34/50 pts #AACR16
9:35am April 19th 2016 via Hootsuite
Swanton: So ctDNA collabs with Natera (Zimmerman), can prediction of branches be made? Detect SNVs in ctDNA #AACR16
9:34am April 19th 2016 via Hootsuite
Swanton: Shows graphic of branching, selective sweeps, longitudinally is difficult. Sequencing only a fraction of tumor DNA #AACR16
9:33am April 19th 2016 via Hootsuite
Swanton: Illusion: a selective sweep. Showing evidence of pos and neg selection in genes, ID'ing potential novel drivers #AACR16
9:32am April 19th 2016 via Hootsuite
Swanton: Tier-1 events: busy map shown for n=100; clonal, subclonal, by mutation and sample. 3rd "illusion of clonality" #AACR16
9:30am April 19th 2016 via Hootsuite
Swanton: 15% of KRAS in some regions and not others; others are 'almost always branched' - Histone mods, DNA repair #AACR16
9:29am April 19th 2016 via Hootsuite
Swanton: BRAF, EGFR activating muts occur before GD; explaining efficacy of Rx #AACR16
9:28am April 19th 2016 via Hootsuite
Swanton: Timing somatic mutations in relation to GD (genome doubling) and tumor branching, looking at a 'rule book' for tumor evol #AACR16
Swanton: Others mitotic-clock. Interest in genome doubling, '13 Nature Gen https://t.co/ZcF5k8k2WS Allowing further branches #AACR16
9:26am April 19th 2016 via Hootsuite
Swanton: Spontaneous deamination of C-T; APOBEC C-T, also smoking signature. #AACR16
9:24am April 19th 2016 via Hootsuite
Swanton: NSCLC, map of first trunks and branches: some with high subclones, others w/fewer. #AACR16
9:23am April 19th 2016 via Hootsuite
Swanton: Unpublished data of first n=100; untreated lung ca. Heavily skewed toward early-stage lung ca smokers #AACR16
9:22am April 19th 2016 via Hootsuite
Swanton: Parallel or convergent evolution; seeing order of events; common founder events. Later driver events, subclonal expansion #AACR16
9:21am April 19th 2016 via Hootsuite
Swanton: Understand tumor heterogeneity, to outcome. Origins of cancer subclones, rel's to CTCs and ctDNA, time somatic events #AACR16
Swanton: TRACERx - 842 pt study, with spatial and temporal tumor genomic analyses. Collect ctDNA, drug resist, consent to autopsy #AACR16
9:19am April 19th 2016 via Hootsuite
Charles Swanton (UCL UK) Tracking cancer evolution through therapy (TRACERx): Implications for immune targeting and surveillance #AACR16
9:18am April 19th 2016 via Hootsuite
RT @SusanDFCI: VP Biden takes part @AACR Conference: Key moment for cancer research https://t.co/njTRtidpoJ #AACR16
8:55am April 19th 2016 via Hootsuite
SeraCare Launches Expanded Offering of Biosynthetic Somatic Tumor Reference Materials for NGS-based https://t.co/5fIOhfdSoA #AACR16
8:53am April 19th 2016 via Hootsuite
Hanahan: '13 Lancet ref https://t.co/sJSgIm8eO3 Immuno, onco-drivers, angiogenesis Sept '16 conference: https://t.co/prwJzigCW3 #AACR16
8:47am April 19th 2016 via Hootsuite
Hanahan: Can envision a 'battlespace' plan for future cancer Rx - combination, layers, sequences of targeting #AACR16
8:46am April 19th 2016 via Hootsuite
Hanahan: Some survival benefit w/this approach. Can 4 hallmarks be targeted? 'A hypothesis yet to be tested' #AACR16
8:45am April 19th 2016 via Hootsuite
Hanahan: Rapalogs may target deregulating energetics, resisting cell death. But survival trials - Rapamycin, Sutent, not curative #AACR16
8:42am April 19th 2016 via Hootsuite
Hanahan: Seeing other work supporting hypothesis in br ca, and PDXs (in press from others). #AACR16
8:41am April 19th 2016 via Hootsuite
Hanahan: anti-angiogenic Rx, comb. w/mTOR inh to disrupt symbiosis. Glut1/Mct4 (up) and Mct1 + mTOR (down) form of adaptive resist #AACR16
Hanahan: Shows data suggestion mTOR activity in MCT1+ cells results in symbiotic support for MCT4+ cells #AACR16
8:39am April 19th 2016 via Hootsuite
Hanahan: Looks at lactate metabolism: in normoxic lactate is catabolized, but not hypoxic cancer cells #AACR16
8:33am April 19th 2016 via Hootsuite
Hanahan: Shows focal clusters of mTOR activity active in non-hypoxic tumor regions. Hypothesis: metabolic symbiosis #AACR16
8:31am April 19th 2016 via Hootsuite
Hanahan: It enhances efficacy, but these tumors are not going away, mice are not cured. Clue: sunitinib upregulates mTOR #AACR16
8:25am April 19th 2016 via Hootsuite
Hanahan: Can invasiveness and angiogenesis be co-targeted? '12 Cancer Disc https://t.co/d0KiaT93bB dual inh of c-Met, VEGF/VEGFR #AACR16
8:24am April 19th 2016 via Hootsuite
Hanahan: '09 ref https://t.co/TuqKaZKRwO an example of hallmark switching - from angiogenesis to activating invasion / metastasis #AACR16
8:22am April 19th 2016 via Hootsuite
Hanahan: A few years at prior AACR mtgs, many sessions about anti-angiogenesis... evasion mechanism is heightened invasion #AACR16
8:21am April 19th 2016 via Hootsuite
Hanahan: Reality check: in anti-angiogenic Rx, unconventional evasive (adaptive) resistance '08 Review https://t.co/Fr5KiAlgqZ #AACR16
8:19am April 19th 2016 via Hootsuite
Hanahan: Now approved for PNET (pancreatic neoendocrine tumors), one of the first new treatments in 25y #AACR16
8:18am April 19th 2016 via Hootsuite
Hanahan: Kinase inh sunitinib (VEFR and PDGFR targeting), shows vascularity reduction, disrupting pericyte coverage #AACR16
8:17am April 19th 2016 via Hootsuite
Hanahan: Role of VEGF-A '02 Cancer Cell https://t.co/3g0zMZAOi9
8:15am April 19th 2016 via Hootsuite
Hanahan: Angiogenic switch - discrete, rate-limiting step in multi-step tumorigenesis '96 Cell https://t.co/mCal0LcbBJ #AACR16
Hanahan: No magic bullets. At CSHL, he built a mouse model for panc ca 30y ago https://t.co/24MI8jlGq4 And still used today #AACR16
8:13am April 19th 2016 via Hootsuite
Hanahan: BRAF inh in melanoma - resistance to trtmt shows after 6mos. For BRAF inh, EGFR inh, angiogenesis, also immune chkpts #AACR16
8:11am April 19th 2016 via Hootsuite
Hanahan: Overall, targeting individuall hallmarks 'hasn't worked very well'. Shows illus from '12 BMC https://t.co/T4T2vj6a3a #AACR16
8:10am April 19th 2016 via Hootsuite
Updated Hanahan #AACR16 Hallmarks slide https://t.co/W8KSRv1xFu
Hanahan: How to apply this concept to more effectively treat cancer? "The jury is still out, no compelling answers yet" #AACR16
8:08am April 19th 2016 via Hootsuite
Hanahan: Reviews figure from '00: 8 hallmarks, from proliferative signalling through energetics #AACR16
