War on cancer: Notes from the frontlines
November 24, 2013
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Last month, I was fortunate enough to attend the tumor heterogeneity and plasticity symposium. The conference which was jointly organized by CNIO and Nature, was held in Madrid. I thought it would be a good idea for me to write some notes on what I heard at the conference.
- There were two keynote speakers, Kornelia Polyak from Dana Farber and José Baselga from across the street from us at MSKCC. Jose’s talk was very much clinical as he enumerated the MANY trials that they are conducting. Kornelia’s talk, on the other hand, was more basic-research-y (is that a word? if not, it should be…). I really cannot distill down a whole keynote into a few sentences, but the bottom-line was: (i) diversity is bad; (ii) we can develop rational experimental approaches to find cancer drivers that are sub-clonal; (iii) sub-clonality brings forth the idea of growth-promoters vs. competitors. All in all, a very good and complex talk… Maybe one of the few talks at the conference with significant mechanistic and functional observations.
- The field, given how young it is, is very descriptive. It largely involves researchers making cool observations… don’t get me wrong, I don’t mean it in a derogatory sense; what I am trying to say is that it would probably take years before we can make sense of many of the observations.
- On the sequencing side, Elaine Mardis talked about very deep whole-genome sequencing of matched primary and metastatic tumors, followed by rigorous validations of each genetic variation. She talked about tumor lineage and pressures exerted by therapeutic manipulations and how they shape the heterogeneity of the metastatic sites. One interesting thing that she mentioned was that very few single-nucleotide variations are actually expressed (I think she said something like 44%).
- Sean Morrison gave a very rigorous presentation on heterogeneity and metastasis. He had used genomic tools plus xenografting in NSG mice to study melanoma.
- Dana Pe’er talked about analyzing mass-cytometry (Cy-TOF) data using ViSNE. Cy-TOF follows the same logic as FACS, with the main difference that instead of fluorophores, other elements with distinct and sharp mass-spec peaks are conjugated to antibodies. About 40 markers can be measured simultaneously for each cell (compared to 7-8 for FACS). However, making sense of a 40-dimensional dataset is not straightforward, which is why ViSNE comes into play. This tool however, can be used for other types of dimensionality reduction approaches as well. Think of it as non-linear PCA…
- Charles Swanton spoke about spatial heterogeneity in tumors where multiple biopsies from the same tumor were sequenced. The level of heterogeneity was scary… For example, we find driver mutations based on their clonality and we aim to target them therapeutically, but there were sub-populations in the tumor that had already lost the driver mutations even in the absence of therapeutic selection pressure.
- A number of speakers touched on this idea that the resistant population is already present in the primary tumor and does not necessarily arise after treatment.
All in all, I met some new people and listened to some amazing talks…