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Promoting Excellence in UK Cancer Research Dr Angela Kukula The Institute of Cancer Research, London Outline 1 Recent advances in cancer research and treatment 2 Translating research into patient impact 3 Accommodating future advances 2 3 Research Excellence and Impact • Ranked first in the Times Higher Education league table of university research quality – based on peer reviewed Research Excellence Framework (REF 2014) • Top for both excellence and impact • We came joint top of academic research institutions worldwide in the Times Higher Education/ Elsevier table for Innovation – based on the proportion of our research papers cited in patents • We were awarded the UK’s only Regius Professorship of Cancer Research by the Queen in 2016 • Together with The Royal Marsden we are rated in the top four Cancer Centres globally measured by citation impact (Thomson Reuters) • We have identified 20 potential new cancer drugs since 2005, with 9 entering clinical trials and 1, abiraterone, approved. 4 5 1 2 3 Recent advances in cancer research and treatment Extraordinary advances in understanding cancer biology Hallmark traits of cancer Hanahan & Weinberg Cell 100 57-70 2000 Cancer genes & pathways Vogelstein et al 339 1546-58 2013 6 Cancer gene sequencing Identifying and targeting individual patient mutations both in the original tumour and throughout therapy 7 Circulating DNA and tumour cells • Circulating tumour cells (CTCs) are cells that have shed into the blood stream or lymphatic system from a primary tumour and are carried around the body in the circulation • Numbers are very small • Capture and characterisation allows monitoring of tumour treatment, evolution and development of resistance in real time 8 9 Precision Medicine Drugging hallmark traits We have seen some exciting new targeted therapies developed for cancer. Each new targeted drug teaches us more about how cancers develop and respond to treatment, and increases the chances of creating better drugs or treatment combinations. Hanahan & Weinberg Cell 144 646-674 2011 Immuno-oncology • Over 100 years old – Coley toxins • Monoclonal antibodies • Transtuzumab (Herceptin) • Immune checkpoints • PD1 receptor inhibitors (Keytruda) • Conjugated antibodies • Ado-trastuzumab emtansine (Kadcyla) • Vaccines • Preventative – HPV • Treatment – sipuleucel T (Provenge) 10 Immuno-oncology • CAR T cells Dramatic results in haematological cancers Recent evidence of utility in solid tumours 11 Radiotherapy developments START trials The START trials looked at radiotherapy dose schedules in women with early-stage breast cancer. Using fewer, larger fractions gave comparable levels of cancer control. The study has had widespread impact on international clinical practice. In the UK, we are now using 250,000 fewer fractions of radiotherapy each year, saving the NHS £50 million per year. 12 Radiotherapy developments MR-Linac • Technical radiation development will increase cure rates of curable cancers and reduce toxicities. • MR-Linac – a game changer that will also open up new indications in tumours that have been traditionally regarded as off limits. • Software solutions to RT planning and RT delivery will significantly improve our ability to treat curable cancers. 13 14 Analysis of pan-cancer sequence data Workman & Al-Lazikani Nat Rev Drug Discov 12 889-90 2013 Large-scale omics • Hypothesis-driven • Functional screens Identifying cancer driver genes Frequency ‘Mountains’ • Non-oncogene addiction Objective assessment of cancer drivers 58 persistent drivers Genes 8 Drug targets 17 With drug-like bioactive compounds 138 25 No current evidence for druggability 11 9 60 58 10 385 513 • Network biology 127 TCGA pan-cancer drivers 11 Drug targets High 32 With drug-like bioactive compounds 14 Druggable 8 Druggable Alternative studies • Synthetic lethality ‘Hills’ Evidence for target being actionable Genome sequencing 50 127 70 No current evidence for druggability TCGA pancancer Drug discovery and development Personalized cancer therapy Low Diagnostic and prognostic biomarkers Patient stratification Challenges we still need to overcome in cancer treatment • Many targeted cancer drugs are effective initially, only for drug resistance to develop • Tumours are extremely genetically diverse, and can evolve dynamically over time – survival of the nastiest • Tumour evolution is forcing us to develop new approaches to treatment to ensure we stay ahead of drug resistance 15 Overcoming this challenge Innovation in cancer treatments • Using targeted drugs in combination or with other treatments including radiotherapy and immunotherapies • Network drugs tackle more than one cellular signaling pathway and hit cancer harder • Circulating tumour cells and DNA allows us to monitor genetic changes within patients over the course of their treatment. 16 Earlier detection • Alongside innovation in treatment we also need innovation in detection technologies •Both detection of the primary tumour and detection of developing resistance or metastases •Every cancer is curable – if we find it soon enough. 17 18 1 Innovation in science and medicine 2 Translating research into patient impact 3 Our partnership with The Royal Marsden • ICR’s partnership with The Royal Marsden forms one of the largest comprehensive cancer centres in Europe • Spanning basic cancer research to practicechanging trials and specialist healthcare • Facilitates our rapid ‘bench-to-bedside and back’ approach Together we are rated in the top four comprehensive cancer centres worldwide for impact on cancer research and treatment – Thomson Reuters Making the discoveries Our strategy to defeat cancer The ICR and The Royal Marsden have worked together on a joint strategy covering the next five years. Our vision We will overcome the challenges posed by cancer’s complexity, adaptability and evolution through scientific and clinical excellence, innovation and partnership. . 20 Making the discoveries The four pillars of our strategy 1 2 3 4 Unravelling cancer’s complexity We will comprehend the full complexity of cancer by harnessing the power of new technologies and Big data. Innovative approaches We will take on the challenge of cancer’s complexity, evolution and drug resistance through the discovery of innovative new approaches to cancer treatment. Smarter, kinder treatments We will move a step closer to cure by bringing personalised treatments into the clinic and developing them for patients. Making it count We will deliver better outcomes and improved quality of life for patients by establishing innovative treatments, diagnostics and strategies for prevention as part of routine healthcare. 21 Working in partnership • • Working in partnership both with other academic institutions and with industry is positively encouraged It is essential to bring together complimentary skills and expertise to allow us to bring our discoveries to patients faster 22 The London Cancer Hub A global centre for cancer innovation 23 The London Cancer Hub aims to create a world-leading life-science campus specialising in cancer research, healthcare, education and biotech innovation. We will provide state-of-the-art facilities, and be joined by a series of high-tech enterprises in a network of 10,000 researchers, clinical staff and support staff all operating from one site. We plan to deliver an exceptional environment for cancer research that enhances the discovery of new treatments and their development for patients 24 1 Innovation in science and medicine 2 Is innovation currently affordable? 3 Accommodating future advances Why are the costs of innovation so high? 25 • Targeted treatments work in smaller patient populations than the blockbusters of the past. The risks remain high while the potential returns are lower. • The drugs coming through are just too expensive for health care systems. Innovation is coming to be seen as unaffordable. • This in turn acts as a disincentive for drug companies to innovate in small populations. • We need to reduce costs by approving and running smaller, smarter, more stratified trials – and passing the costs savings down the line. Approvals for innovative trials 26 Willingness of the pharmaceutical industry to embrace new trials designs Risk sharing approaches that make it easier for companies to take risks A price system that is affordable and incentivises innovation A regulatory system which allows innovative approaches and early adoption of new medicines Evaluation systems which recognise innovation Combination treatments • Using rational combinations of drugs against same or several pathways at once has the potential to address tumour heterogeneity and evolution • But use of combinations poses challenges in: • trial design • approvals • “real time” combination prescribing • price If we are to see improvements in survival and cure rates we need to improve the affordability and accessibility of combination therapies. 27 Drug pricing We need to build confidence that health systems will pay for the most innovative and effective cancer treatments. Innovation needs to be embedded throughout the whole process of bringing a drug to market, including at the drug approval and cost evaluation stage. We need innovative ways of pricing combination therapies As regulators increasingly approve drugs based on phase 2 data we need pricing models that can accept this immature overall survival data 28 Scientific opportunities for innovation • Basic, translational and clinical research are all important in understanding cancer and improving treatments. • Research looking more comprehensively at cancer on a network or systems level is increasingly becoming important. • Major breakthroughs in understanding cancer will continue and we will overcome clonal evolution and drug resistance – and find ways to stay ahead of cancer. •But we must find ways to ensure that these innovations are available to health care providers at an affordable price. 29