Charlotte Proudhon (Institut Curie, Paris) Patient-specific ctDNA detection during neoadjuvant chemotherapy of TNBC #MAPonco16
8:41am September 24th 2016 via Hootsuite
Voest: PIFAs alter DNA damage resp induced by cisplatin (and other genotoxic chemo) #MAPonco16
8:24am September 24th 2016 via Hootsuite
Voest: Mesemchymal Stem Cells: 4y of work in 1 slide: https://t.co/5WJLUDHZxx Recommend no fish oils for cancer pt (PIFAs) #MAPonco16
8:23am September 24th 2016 via Hootsuite
Voest: With EGFR inhibition, shows graphic 'accepted collateral damage'. Complex fig from https://t.co/2BXfK7q1qF #MAPonco16
8:20am September 24th 2016 via Hootsuite
Emile Voest (Antoni van Leeuwenhoek, Netherlands) Metabolic changes due to DNA repair defects #MAPonco16
8:18am September 24th 2016 via Hootsuite
Nik-Zainal: Finishes w/several examples of MMR-deficient breast cancer cases Credits ICGC Breast Cancer Working Group. #MAPonco16
8:14am September 24th 2016 via Hootsuite
Nik-Zainal: (And she points out she's a black belt, DO NOT MESS WITH HER. Public service announcement.) #MAPonco16
8:04am September 24th 2016 via Hootsuite
Nik-Zainal: Talks about unpublished data, no photos or tweets. Some great work though with a new unpublished tool. #MAPonco16
8:03am September 24th 2016 via Hootsuite
Nik-Zainal: Of 560 women, 'no two women have identical signatures' #MAPonco16
7:54am September 24th 2016 via Hootsuite
Nik-Zainal: Of about a total of about 40 known signatures across cancer types, roughly half have unknown etiology #MAPonco16
Nik-Zainal: Sig 1 is C->T; five sigs with SNVs; add'l five are rarer, low-freq. Shows frequency by color of signature #MAPonco16
7:53am September 24th 2016 via Hootsuite
Nik-Zainal: Illustrates mutation over time from fertilization of egg through development of cancer. Describes signatures #MAPonco16
7:50am September 24th 2016 via Hootsuite
Nik-Zainal: Recurrent mutations in non-coding sequence: nothing actionable, you will find events. HG is 'Fantastically complex' #MAPonco16
7:47am September 24th 2016 via Hootsuite
Nik-Zainal: 560 breast ca WGS; 3.4 SNVs, 371K small indels; 77.6K rearr's. About 1,628 total drivers. 62% of drivers in top10 #MAPonco16
7:46am September 24th 2016 via Hootsuite
Serena Nik-Zainal (Wellcome Trust, UK) Advances in the understanding of mutational processes #MAPonco16
7:44am September 24th 2016 via Hootsuite
Swanton: ... and the accelerated pace is not captured, a PFS2 or PFS3 measure #MAPonco16
7:43am September 24th 2016 via Hootsuite
Swanton: Raises the spectre of 'competitive release of resistant subclones' where PFS doesn't capture accelerated pace of disease #MAPonco16
7:42am September 24th 2016 via Hootsuite
Swanton: Why is it so difficult to improve Overall Survival? Cross-over from placebo/std of care to active drug; pretrtmt #MAPonco16
7:41am September 24th 2016 via Hootsuite
Swanton: Finding neo-antigen-reactive T-cells (NAR-T) in NSCLC to target runcal muts '14 Nature Meth https://t.co/NOH4taAwWu #MAPonco16
7:39am September 24th 2016 via Hootsuite
Swanton: Analysis of PD1 response in NSCLC by neo-antigen clonal/subclonal status #MAPonco16
7:36am September 24th 2016 via Hootsuite
Swanton: Chromosomal instability 'is a major determinant of outcome', not SNV heterogeneity #MAPonco16
7:30am September 24th 2016 via Hootsuite
Swanton: KRAS G12C is good, but a second hit (G12K) now fully independent. No relapse yet in pt, but sequential activation #MAPonco16
7:27am September 24th 2016 via Hootsuite
Swanton: Looking at early EGFR BRAF trunk initiating driver events, and genome doubling. One case: sequential KRAS driver #MAPonco16
7:26am September 24th 2016 via Hootsuite
Swanton: p53 wt cells with genome doubling '14 Cancer Disc https://t.co/WBoAS76fhZ Obs in 80% of NSCLC TRACERx cases #MAPonco16
7:22am September 24th 2016 via Hootsuite
Swanton: Chromothripsis, chromoplexy, genome doubling, sructural CIN. Doubling - accel. cancer genome evolution #MAPonco16
7:21am September 24th 2016 via Hootsuite
Swanton: Other colors - smoking (grey), age (blue), unknown (green). Onto Macroevolution: chromosomal rearrangements #MAPonco16
7:20am September 24th 2016 via Hootsuite
Swanton: Shows 100 trees on a slide; but the datasets are 'massive' too large to capture visually. Impt: color (yellow=APOBEC) #MAPonco16
7:18am September 24th 2016 via Hootsuite
Swanton: Smoking mutations and length of trunk - a clear driver of trunk size. A cancer stem-cell pool exposed to mutagens #MAPonco16
7:16am September 24th 2016 via Hootsuite
Swanton: Spontaneous deamination (C->T), APOBEC '13 ref https://t.co/gNTCjA94d0 and mitotic clock #MAPonco16
7:15am September 24th 2016 via Hootsuite
Swanton: Wide range of phylogenetic trees; overlaying CNAs, there may be 'overlaid prognostic implications' #MAPonco16
7:14am September 24th 2016 via Hootsuite
Swanton: First 100 pts: 'typical': 94% have smoked; 6 lifetime non-smokers. NSCLC: coding muts as clonal or heterogeneous. #MAPonco16
7:12am September 24th 2016 via Hootsuite
Swanton: All the way through to death. Figure of different trees; '12 STM ref https://t.co/2qq1XQGjiU #MAPonco16
7:11am September 24th 2016 via Hootsuite
Swanton: TRACERx update (from CRUK blog) https://t.co/ZPUOyFU91N Multiple biopsies, n-842, spatial, temporal analyses #MAPonco16
7:09am September 24th 2016 via Hootsuite
Swanton: Want to target trunk effects, as well as look at branched. 10 patients branching trees - Ubiquitous, shared, private #MAPonco16
7:07am September 24th 2016 via Hootsuite
Charles Swanton (CRUK): Clinical implications of ITH and Cancer Evolution #MAPonco16
7:05am September 24th 2016 via Hootsuite
Remon: n=174, used Inivata's service, 50% of mutations <1% mutant allel frequency. 17% of pts 'rescued' since now actionable Rx #MAPonco1
6:24am September 24th 2016 via Hootsuite
Remon: 25% of pts have no molecular profile. '16 Lancet https://t.co/gHSXy6S0e3 #MAPonco16
6:21am September 24th 2016 via Hootsuite
Jordi Remon (Gustave Roussey / Inivata) New Applications for ctDNA #MAPonco16
6:20am September 24th 2016 via Hootsuite
Bardelli: Clinical trial called CHRONOS, funded and enrollment open. Section on RAS prevalence, and concomitant EGFR #MAPonco16
6:12am September 24th 2016 via Hootsuite
Bardelli: 'These are disappointing stories' - the heterogeneity of primary tumors; acquiring resistance. Thus: target cancer evol #MAPonco16
6:05am September 24th 2016 via Hootsuite
Bardelli: HERACLES trial on HER2 in mCRC in recent Lancet Oncol https://t.co/lgr2xGPjmq #MAPonco16
6:01am September 24th 2016 via Hootsuite
Bardelli: ALK, MET, HER2, EGFR, TRKA, Wnt1, RSPO - and all the drugs that target. HER2 in CRC in PDX, dual-blockade #MAPonco16
5:59am September 24th 2016 via Hootsuite
Bardelli: 10y ago, there were a lot of markers, but nothing making it to the clinic. Now a lot of actionable targets #MAPonco16
5:58am September 24th 2016 via Hootsuite
Bardelli: Progression cartoon of CRC - early hyperproliferation can be detected. (progress to adenoma, to polyps, to displasia #MAPonco16
5:56am September 24th 2016 via Hootsuite
Alberto Bardelli (IRCC Univ Torino, Italy) Cancer evolution as a therapeutic target #MAPonco16
5:55am September 24th 2016 via Hootsuite
Turner: One challenge - differentiate 'normal' clonal expansions from early-stage cancer. #MAPonco16
5:54am September 24th 2016 via Hootsuite
Turner: Looking in blood - TP53 found '16 PNAS https://t.co/RBz7KvxNng Old test '06 NEJM https://t.co/FCC7G32sXy Not useful #MAPonco16
5:53am September 24th 2016 via Hootsuite
Turner: #MAPonco16 Shows data from normal skin mutations '15 Science https://t.co/HqL4Jj9nXt 'you find them all over your skin'
5:50am September 24th 2016 via Hootsuite
Turner: And by age: by 65y, 10% had clonal hematopoesis, with much higher risk of heme cancers. Showed survival curves #MAPonco16
5:49am September 24th 2016 via Hootsuite
Turner: These mutations were DNMT3A, and along list of known drivers. Looked across time and found >3 somatic muts #MAPonco16
5:48am September 24th 2016 via Hootsuite
