WIN 2017

Dr Büttner speaks with ecancer at WIN 2017 about determining vulnerabilities to targeted or immune therapeutics in lung cancer through Network Genomic Medicine. He discusses the landmark successes of PD-1 checkpoint therapy for lung cancer, and futher mutational markers of resistance and vulnerability. Dr Büttner considers the comparable incidence of lung cancers resulting from germ-line mutation and those arising from environmental factors, with emphasis on early detection and diagnosis to alleviate disease burden before advanced disease

Prof Baynes speaks with ecancer at WIN 2017 about design and development of immune therapies sensitive to mutational deficiencies in the DNA repair pathway He notes the recent approval of pembrolizumab (Keytruda) PD1 therapy for relapsed cancer patients with a high mutational burden determined with a micro-satellite instability assay. Prof Baynes outlines the ongoing trials combining checkpoint immunotherapy with targeted agents such as tyrosine kinases, radiotherapy and chemotherapy, including results alongside other immuno-modulatory agents such as oncolytic viruses.

Prof Bernards speaks with ecancer at WIN 2017 about a staggered '1-2 punch' treatment schedule of cancer therapies, built on synthetic lethality. In the case of BRAF melanoma, he describes the acquired MEK-resistance of tumour cells following initial treatments exposes vulnerability to histone deacetylases (HDAC) which generate a toxic level of reactive oxygen species (ROS) in cancer cells. Prof Bernards outlines how intermittent dosing cycles with short HDAC therapies 'chasers' may prevent further resistance development and extend patient survival. He goes on to explain the best treatment window for selectively targeting cancer cells follows an induced senescence, with animal models currently in development.

Dr Bristow speaks with ecancer at WIN 2017 about trials ongoing with patients in the Canadian Prostate Cancer Genome Network (CPC-GENE) to determine patient subgroups most at risk of disease progression and drug resistance. He notes the use of imaging to guide treatment and gauge response, and considers the significance of the abiraterone data from earlier this year at ASCO 2017.

Dr Kurzrock speaks with ecancer at WIN 2017 about the mismatch between current clinical trial design and the breadth of patient data accessible over the course of personalised treatments. She highlights advances in liquid biopsy technology and computerised analysis as key to ongoing, up-to-date insights from a patient's tumour genome, and discusses how reporting of the outcomes from last years SHIVA trial fails to reflect the data generated.

Dr Kallioniemi speaks with ecancer at WIN 2017 about his research in developing targeted therapies for leukaemias, among other diseases. He describes the need for data integration into healthcare processes to deliver significant, actionable data within a useful time frame, and how serial biopsies can undermine any resistance mutations as they arise. Dr Kallioniemi notes the repositioning of axitinib for drug resistant leukaemia based on drug resistance as an example of how screening of tumours can inform treatment selection, foregoing the regulatory hurdles of developing a new therapy.

Dr Lichter speaks with ecancer at WIN 2017 about germline mutations and heritable predispositions behind in paediatric brain cancer. He outlines the Sonic Hedgehog family of genes as common driver in medulloblastoma, and discusses how translocation of genes to enhancer regions can trigger disease onset. Dr Lichter notes that guidelines for treatments must reflect mutational subtypes, with patients whose tumours show enhanced activation of Wnt-Catenin signalling among the best prognosis compared to APC and Sonic subtypes.

Prof Piccart speaks with ecancer at WIN 2017 about issues facing translational research, and the need to look beyond individual biomarkers to characterise a whole-cell understanding on cancer. She outlines her priorities in determining how chemotherapy regimens could be reduced or phased out entirely with immune therapies, and considers how ongoing surveillance of tumour genomics may offer immediate insight into treatment response.

Prof Hood speaks with ecancer at WIN 2017 about predictive, preventive, personalised, participatory healthcare in his P4 Medicine Institute, and measuring what he terms Scientific Wellness. He outlines how systems medicine and ongoing surveillance of genotyping may reveal the stages at which disease begins, spreads and evolves, as well as providing insight into treatment response and ongoing recovery. Prof Hood considers the importance of keeping a patient's humanity at the centre of their genomic data, with psycho-social training to encourage lifestyle approaches to disease management.

Prof Baselga speaks with ecancer at WIN 2017 about widening trial targets and patient participation for new therapies against breast cancer. He introduces phase I studies of taselisib, now escalating to a phase III study (SANDPIPER) combining the PI3K inhibitor with fulvestrant, aiming to improve specificity and toxicity compared to previous studies. Prof Baselga discusses Akt inhibitors as single agents and used alongside immunotherapies, and a network to streamline patient recruitment to relevant clinical trials.

Prof Blay speaks with ecancer at WIN 2017 about open questions and the future of research in immunotherapy. Among the avenues to explore, Prof Blay outlines the variation in patients response rates and duration, with hyper-progressors posing as much a mystery as best responders. He lists multiple subtypes across diseases, offering a vast ocean of disease stratification that may never be fully charted, but notes that innovations in trial design and treatment combinations offer chances of achieving the most benefit for even rare diseases. Prof Blay notes changing availability and cost of genome sequencing and liquid biopsy as opening new futures in bioinformatics, with physics and mathematics coming to the fore in biological understandings of disease and data.

Dr Lee speaks with ecancer at WIN 2017 about changing attitudes and designs of trial design to a Bayesian framework, which integrates serial data collection into the assessment of patient response. He notes 20% of trials conducted at M.D. Anderson incorporate some elements of Bayesian design, including the I-SPY 2 trial.

Dr Rodriguez speaks with ecancer at WIN 2017 about the translation of the proteins expressed in a patient's tumour into a map for druggable targets. He highlights aspects of the Beau Biden Cancer Moonshot initiative, working with the National Cancer Institute, which aim to open global access to data libraries of tumour genomics and proteomics, including the APOLLO program and the International Cancer Proteogenome Consortium.

Prof Rammensee speaks with ecancer at WIN 2017 about assessing the human leukocyte antigen (HLA) rearrangements of cancer patients to determine new targets for therapies. He summarises the 'ligandome' and its role in directing T cell response, noting mutation-high tumours responding more to checkpoint immunotherapy, and describes how peptides derived from ligand assays could help design cancer vaccines.

Dr Massimini speaks with ecancer at WIN 2017 about novel drugs suitable as monotherapy or in combination to inhibit DNA repair pathways in tumours. He highlights VX970 / M6620, a novel drug affecting the ATR kinase pathway of DNA repair, as well as M3814 which is currently in assessment combined with radiotherapy, and considers class-associated toxicities of DNA repair pathway inhibition.

Prof Ribas speaks with ecancer at WIN 2017 about "the canary in the mine" of PDL-1 expression on tumour cells, and their response to checkpoint therapy. He notes the off-target toxicities of ipilimumab, and the rationale for combining therapies to increase T cell infiltration beyond CTLA-4. Prof Ribas notes the importance of the tumour microbiome in determining immunotherapy response, and the differing outcomes of adjuvant vs neoadjuvant staging.

Dr Hayes speaks with ecancer at WIN 2017 about ease of use and wealth of information made possible with liquid biopsy to derive tumour genomics. He describes the utility of serial biopsies in guiding patients selection of treatment or trial participation, and also how interrogation of this data may determine suitable biomarkers for further research, or reveal the development of resistance pathways in real time. Dr Hayes considers the use of circulating biomarkers as surrogates for clinical endpoints, and contemplates the historic context of personalised therapy from the first vaccines to the current understandings of tumour heterogeneity.

Prof Robert speaks with ecancer at WIN 2017 about tackling class-associated toxicity and drug resistance with combination therapies based on tyrosine kinase inhibition.