Cancer Network Newsletter July - August 2018

£1.4m to investigate cancer growth Inside this issue:

Prof Eugenia Piddini mal cells plays a pivot- have also revealed Events 2-3 (CMM) has been al role in cancer how it is possible to awarded a Pro- growth, and that contain the growth of News 4-10 gramme Foundation better understanding these cancers by pro- Award worth £1.4 mil- the nature and impact tecting normal cells EBI Funding 11 lion by Cancer Re- of this exchange is key from cell competition search UK (CRUK) to to identifying novel and therefore from Funding Opps 12-13 lead research into anti-cancer strategies. being killed by the Featured how the natural prop- Using Drosophila Prof cancer. The CRUK 14 erties of normal non- Piddini’s group have award will fund Prof Publication cancer cells can be shown that cancer Piddini’s research for harnessed to contain cells compete with the next 6 years to Contacts 15 cancer growth. and kill neighbouring investigate further the normal ‘host’ cells, impact that interfering Cancer has become known as “cancer- with cell competition one of the most com- host cell competition”. has on cancer growth. @BristolCancer mon and deadly dis- They have shown that Image shows intestinal eases. It is becoming the process fuels can- cancer-research tumour masses (green) increasingly clear that cer growth by allowing @.ac.uk growing and expanding the communication cancer cells to clear a in the intestinal cavity of between cancer cells bristol.ac.uk space that they can a fruit fly (red). © Pid- and surrounding nor- expand into. The team dini Group /cancer

+44 117 428 4012 Page 2

EVENTS

L&R Postgraduate seminars 24 July 2018, 13.00 - 14.00, Yunfei Li (Year 1, PhD student): Development and validation of a new ex-vivo model for the study of osteoarthritis using human osteochondral plugs, and Reham Mashat (Year 2, PhD student): The role of 27-Hydroxycholesterol in breast cancer cell line. Seminar rooms A&B, Level 2, Learning and Research Building, Southmead Hospital

Translation Toolkit seminar series: Why Science Policy Matters 7 July 2018, 14.00 - 15.00, Rhiannon Wilson (PolicyBristol) and Dr Hannah Rose-Vineer (Bristol Veterinary School, pictured top right), G13/14 Life Sci- ences Building

Infection and Immunity Early Career Researchers' Symposium 10 September 2018, 9.45 - 14.00, Life Sciences Building

Cancer in Children and Young People Conference 12 - 14 September 2018, Westminster, London

IDEAL International Conference 13 - 14 September 2018, MShed, Princes Wharf, BS1 4RN

Translation Toolkit seminar series: How to be an Effective Networker 13 September 2018, 14.00 - 17.00, Vox Coaching, venue TBC

CITER Annual Scientific Meeting 2018 17 - 18 September 2018, Keynote: Dr Rhys Jones (Cardiff University, pic- tured second from top on right), Cardiff University

Translation Toolkit seminar series 27 September 2018, 14.00 - 15.00, venue TBC

UK CLL Forum Clinical Sciences Day 28 September 2018, 9.15 - 17.05, Cavendish Conference Centre, 22 Duchess Mews, London W1G 9DT

Crick Cancer Research Symposium 1 - 2 October 2018, The Institute, London

Early Detection of Cancer Conference 2018 2 - 4 October 2018, Knight Cancer Research Building, 2720 SW Moody Ave., Portland, OR 97201 (USA)

Come and make a Fun Palace 6 - 7 October 2018, various around Bristol

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EVENTS CON’T

Translation Toolkit seminar series 25 October 2018, 14.00 - 15.00, venue TBC

2018 NCRI Cancer Conference 4 - 6 November 2018, SEC Glasgow

The effect of the IGF binding proteins in the progression of breast cancer 6 November 2018, 13.00 - 14.00, Ahmad Alghamdi (Year 3, PhD student), Seminar rooms A&B, Level 2, Learning and Research Building, Southmead Hospital

UK Myeloma Forum Autumn Day 8 November 2018, 9.00 - 16.00, Cavendish Conference Centre, 22 Duchess Mews, London W1G 9DT

Clinical Academics in Training Annual Conference 2018 8 November 2018, 9.30 - 17.30, The Royal College of Physicians Edinburgh

L&R Postgraduate Presentations 13 November 2018, 13.00 - 14.00, Georgina Mortimer (Year 1, PhD stu- dent): Down’s syndrome and diabetes – insights into rapid progression to type 1 diabetes and Amy Howell (Year 1, PhD student): Risk factors for de- velopment and progression of Primary Brain Tumours, Seminar rooms A&B, Level 2, Learning and Research Building, Southmead Hospital

Building collaborations in global cancer care: from fragile conflict ecosys- tems to emerging economies 19 November 2018, 8.00 - 18.00, keynote speakers: Prof Richard Sullivan & Dr Ophira Ginsburg, Royal Society of Medicine, 1 Wimpole Street, London, W1G 0AE

Pumps and Pipes UK Conference 19 February 2019, 8.00 - 18.00, SPE Aberdeen

Biological therapies in cancer - towards cancer cures 7 March 2019, 14.30 - 19.00, Prof (The Francis Crick Insti- tute), The , London

From top: NEWS AND EVENTS ARE REGULARLY UPDATED ON THE Ahmad Alghamdi, CANCER RESEARCH NETWORK WEBSITE Ophira Ginsburg, Richard Sullivan, Charles Swanton Page 4

NEWS

UCRF funded projects

The University Cancer Research inhibition of CARM1 will modu- cent results from our laboratory Fund (UCRF) approved funding late E2F/Myconcogenic tran- suggest that the tumour sup- for five projects in the 2018 scription factors to favour a pressor BASP1 plays a central round: growth suppressive pro- role in the action of the anti- apoptotic signature rather than cancer drug in breast Jon Lane: Autophagy- a proliferation signature. This cancer cells. The purpose of this transcriptional crosstalk in tu- will represent key validation da- proposal is to obtain preliminary mourigenesis: the LMX1A ta for this axis representing a data for a grant application that /LMX1B paradigm. Purpose: To tractable drug target, thus facili- will explore how BASP1 regu- test the hypothesis that the tating future MRC and or CR-UK lates the different effects that ATG8 family of autophagy pro- drug discovery projects. tamoxifen exerts in endometrial teins coordinates the expres- cancer cells. sion of autophagy genes by di- Harry Mellor and Gemma Cass: rect binding to and regulation Title: Markers of response to Kaitlin Wade: The human gut of transcription factors in the bevacizumab in ovarian cancer. microbiome in colorectal cancer: nucleus. Purpose: To identify serum causal effects vs. confounded markers of response to bevaci- relationships. Purpose: To sup- Karim Malik and Madhu Kol- zumab in patients with ovarian port or challenge the role of the lareddy: Establishing CAR- cancer. human gut microbiome in the M1/PRMT4 as a novel drug tar- development of colorectal can- get in high-risk neuroblastoma. Stefan Roberts: The role of cer using applied epidemiology Purpose: RNA sequencing will BASP1 in the response of cancer and Mendelian randomisation establish that pharmacological cells to tamoxifen. Purpose: Re- methodology.

Researcher profile: Sabina Sanghera

In January 2018 Sabina began sessment, recall and the quality- Sabina will be her NIHR post-doctoral fellow- adjusted life year (QALY) calcu- collaborating ship in health economics (01/18 lation on cost-effectiveness rec- with col- - 12/20). The research ommendations when health is leagues from is entitled Accounting for the fluctuating. Sabina will use NICE, Univer- impact of fluctuating health mixed-methods to understand sity of Bristol, states on quality of life how patients complete ques- other Univer- measures included in economic tionnaires, identify how and sities in the evaluation. Using chemothera- when to measure quality of life, UK, and Erasmus University py treatment for cancer as a and investigate the suitability of Rotterdam. Her mentors are Jo- case study, she will assess the current valuation methods in anna Coast, Tim Peters, Dr Axel influence of the timing of as- recurrent fluctuating states. Walther, and Katherine Payne. Page 5

Funding successes

Miss Amy Davies (Bristol Den- date 1 June 2018 for two tal School, pictured below years. right) from the NIHR - Pro- gramme Grant for Applied Dr Abderrahmane Kaidi Research, £9,628 for Head & (Cellular and Molecular Medi- Neck 5000 for one year. cine) from the Leverhulme Trust, £32,068 for Under- Dr Abderrahmane Kaidi standing the role of nuclear (Cellular and Molecular Medi- actin polymerisation in DNA cine, pictured top right) from repair. Start date 1 June 2018 Cancer Research UK, for one year. £176,326 for Understanding and targeting bacterial-driven cancer cell-stemness to over- come chemo-resistance. Start

Fighting cancer with nature

New research led by UoB can- is a natural plant extract that the efficacy of PTL, as well as cer biologists has shown that has previously shown excel- other chemotherapy drugs, by bone marrow cells can protect lent anti-leukaemia activity starving childhood T-ALL cells cancer cells from a plant de- with minimal effects on nor- of anti-oxidants. The next step rived anti-cancer agent called mal blood healthy blood cells. is to fully evaluate if blocking Parthenolide. However, some populations antioxidant release enhances of these cancerous cells un- anti-leukaemia drug effects in Current therapies for children fortunately do remain re- vivo. suffering from an aggressive sistant to Parthenolide. type of cancer found in the Ede BC et al. (2018). Investi- blood, T-cell acute lympho- A new study explores the gating Chemoresistance To blastic leukaemia (T-ALL), mechanisms for this re- Improve Sensitivity Of Child- have increased survival rates sistance. The team found that hood T Cell Acute Lympho- to above 85% in developed protection against PTL is pro- blastic To Par- countries. Unfortunately, vided by the release of antiox- thenolide. Haematologica. some patients fail to respond idants by normal support cells 186700. to therapy and many suffer derived from the bone mar- from serious side effects, row. By blocking the release highlighting the need to inves- of antioxidants a significant tigate other agents to treat reduction in leukaemia cell this disease. resistance to PTL was seen. These findings indicate that it The agent Parthenolide (PTL) may be possible to improve Page 6 Cancer Network Newsletter

Link between obesity and smoking behaviour A study by the International with genetic information on exposure may originate in a Agency for Research on Cancer nearly 450 000 participants. common biological basis for (IARC) provides new evidence Based on genetic markers of addictive behaviours, such as that increased weight and obe- obesity, the study allows us to nicotine addiction and higher sity may result in increased better understand the complex energy intake. smoking. The team found that relationship between obesity increased body mass index and important smoking habits It is known that smokers have (BMI), body fat percentage such as smoking initiation and a lower body weight on aver- and waist circumference were intensity, as well as the impact age than non-smokers, possi- associated both with a higher of obesity on smoking cessa- bly because of a reduced appe- risk of being a smoker and tion, says Dr Paul Brennan. The tite in smokers, but that peo- with greater smoking intensity. study also suggests that the ple tend to gain weight after These results were consistent link between BMI and tobacco quitting smoking. However, in both men and women. among smokers, those who smoke more intensively tend In contrast to previous studies to weigh more. This new anal- evaluating the relationship be- ysis of genetic variants linked tween body weight and smok- to body mass highlights the ing behaviour, this study was complex relationship between based on genetic markers of obesity and tobacco smoking. obesity using UK Biobank data Read more

Health data review

A new landmark report pub- UK, detailing key activities and Primary Care and Joint Head of lished by the MRC highlights ma-jor investments made by CAPC, Bristol Medical School the University’s strengths in UK public funders, govern- (PHS) said: "This is an im- digital health research and ment, charities and universi- portant snapshot of the other areas. ties from across the country. breadth and depth of UK

Health Data Research. The Mapping the Landscape of UK Prof John Macleod, Professor fast-moving nature of this sec- Health Data Research and In- in Clinical Epidemiology and tor means that inevitably the novation is a new landmark report is already out of report published by the date. Bristol's unique Medical Research Council. strengths are clearly de- The review, commissioned scribed and we will contin- in 2017, encompasses 26 ue to grow these and realise research organisations. The their potential for impact on report highlights the com- health improvement". plex and flourishing area of health data research in the Read the full report Page 7

New drug and material discoveries to be untangled in VR

A joint team of computer sci- structure to combine real- breakthrough way to change ence and chemistry research- time molecular simulations how drugs are designed, and ers, in collaboration with de- with the latest virtual reality to transform the teaching of velopers at Bristol based start- technology. This collaboration chemical structures and dy- up Interactive Scientific and has made it possible for re- namics. Anybody wishing to Oracle Corporation, have used searchers to reach out and try out the tasks described in Oracle's public cloud infra- ‘touch’ molecules as they the paper can download the move - folding them, knotting software at them, plucking them and https://isci.itch.io/nsb-imd, changing their shape to test and launch their own cloud- how they interact. Using hosted session. cloud computing, several people can interact with the O’Conor M et al. (2018). Sam- molecules in the same virtual pling molecular conformations space at the same time. and dynamics in a multi-user virtual reality framework. Sci- Industry is already showing ence Advances. 4(6), interest in using VR in this eaat2731.

Research Design Service (RDS) The National Institute for allow RDS advisers in the to support researchers, work- Health Research (NIHR) has South West to continue offer- ing in applied health, across awarded the Research Design ing free and confidential ad- the South West of England and Service (RDS) a further five vice, drawing on a unique to strengthen our engagement years of funding to continue breadth of experience and es- with partners in social care. the work of the RDS South tablished track record in im- West. proving funding applications. Find out more about how the RDS could help you by visiting Proposals were invited from The RDS have been funded for the website or contacting the NHS organisations and Higher the ten years prior to this RDS South West Bristol Office: Education Institutions in Eng- round of funding and the ad- land with proven expertise in vice offered by us to research- The Education & Research research methodology and ers represents a key contribu- Centre - Level 3 design. Ten organisations were tion to the NIHR’s commit- University Hospitals Bristol successful and the combined ment to delivery of high quali- NHS Foundation Trust Research Design Services will ty health and social care re- Upper Maudlin Street form a national network, liais- search. Bristol, BS2 8AE ing with each other to develop Tel: 0117 342 0233 a consistent service to the re- Prof Gordon Taylor, Director Email: [email protected] search community across Eng- of NIHR RDS SW: land. The NIHR funding will We look forward to continuing Page 8 Cancer Network Newsletter

A home medical sensing device?

New research that could trans- the EPSRC, Toshiba and iour patterns play a significant form the future of healthcare Decawave to the OPERA pro- role in a range of long-term will investigate whether it is ject, a consortium including chronic health conditions; the possible to reuse WiFi radio the universities of Bristol and UK currently spends 70% of its waves as a medical radar sys- Oxford; University College Lon- entire health and social care tem. The research is part of a don and Coventry University. budget on these types of con- new £1.5m grant awarded by The 3-year project, starting in ditions. OPERA will attempt to October 2018, will extend build a complementary pas- the current SPHERE project, sive-sensing platform by reus- which is developing sensors ing existing home technolo- for use in the home to spot gies; a receiver-only radar net- health and wellbeing prob- work that detects the reflec- lems, with both projects tions of ambient radio- running until 2021. frequency signals from people. Physical activity and behav- Read more

Screening and treatment for Jenny Donovan, Professor of Testing for Prostate Can- was no difference in mortality Social Medicine, on recent cer (CAP), funded by Cancer between the groups allocated findings from two prostate Research UK and the Depart- to surgery, radiotherapy or cancer trials: ment of Health and Social active monitoring. However, Care. The NIHR-funded Pros- men who underwent radical A recent announcement stated tate testing for cancer and treatments were half as likely that deaths from prostate can- Treatment (ProtecT) trial – the to develop metastases or local cer exceeded those from largest of its type – was em- disease progression compared breast cancer in England and bedded in CAP. The main find- with men who underwent ac- Wales for the first time – ing of CAP was that after a me- tive monitoring (2-3% versus 11,800 per year. Yet screening dian of 10 years’ follow up, 6%). And, for the first time, for prostate cancer is a contro- while the number of cases of ProtecT showed that surgery versial public health topic. prostate cancer was higher in and radiotherapy were equally There are strong advocates for men who underwent screening effective at treating localised or against screening for pros- than in the control group, prostate cancer. tate cancer who draw on the screening had no effect on same evidence to reach oppo- prostate cancer-specific or all- The outcomes of the CAP and site conclusions. The third and cause mortality. Meanwhile in ProtecT trials provide a great largest ever randomised trial the ProtecT treatment trial, deal of information to facili- of prostate prostate cancer mortality was tate individual decision-making was published, the Cluster extremely low at around 1% at and to guide policy and further Randomized Trial of PSA a median of 10 years. There research. Read the full review Page 9

Improving clinical trials

Medicine relies heavily on clin- ing an aggressive form of the tate cancer but rather in- ical trials which, while essen- disease. A UoB team used a creased rates of advanced tial, are extremely costly and set of genetic variants known prostate cancer and type 2 dia- carry the potential of unin- as SNPs to estimate the effect betes. tended adverse consequences. of increasing blood selenium The study showed that there to a similar level as in the trial may have been a way to pre- A study, funded by CRUK, re- to see if they could have pre- dict the SELECT trial results in examined and replicated the dicted these results. advance, and proposes that results of a $115m US trial Mendelian randomisation conducted in 2001 that aimed SNPs affect variations in the could serve as an important to see whether taking vitamin levels of vitamins and minerals time-efficient and inexpensive E or a selenium supplement we hold. The study looked at way of testing interventions could lower the risk of pros- these selenium-increasing for their efficacy and possible tate cancer. The trial had to be SNPs in more than 70,000 men adverse effects prior to the abandoned early due to evi- who had taken part in other design of a randomised trial. dence that men taking vitamin studies, allowing them to rec- The study could have far E supplements were at elevat- reate the groups from the orig- reaching implications for the ed risk of prostate cancer and inal trial. They analysed how way that population health that those taking selenium many of these men had subse- studies are conducted in the were at higher risk of develop- quently developed prostate future. cancer to see what differ- ences there were be- Jarmolinsky J et al. (2018). Cir- tween the groups. As culating Selenium and Prostate with the trial researchers Cancer Risk: A Mendelian Ran- found that genetic vari- domization Analysis. Journal of ants associated with ele- the National Cancer Institute. vated blood selenium lev- Djy081. els did not prevent pros-

Mendelian Randomisation Studies of Cancer Risk Pierce BL et al. (2018). Mende- traits, and/or biomarkers on terest to have known genetic lian Randomisation Studies of cancer risk in humans. Many determinants that can be used Cancer Risk: a Literature Re- such risk factors have been as proxies for the risk factor view. Current Epidemiology associated with cancer risk in (i.e., “instrumental variables” Reports. 5(2), pp184–196. The observational studies, and the or IVs), and these can be used paper summarises prior stud- MR approach can be used to to obtain an effect estimate ies that have used Mendelian provide evidence as to wheth- that, under certain assump- randomisation (MR) methods er these associations represent tions, is not prone to bias to study the effects of expo- causal relationships. MR meth- caused by unobserved con- sures, lifestyle factors, physical ods require a risk factor of in- founding or reverse causality. Page 10 Cancer Network Newsletter

Patient prehabilitation gets a boost

Thanks to initial funding from fitness before a major opera- search for Health Challenge the Elizabeth Blackwell Insti- tion can reduce the risk of scheme in response to a chal- tute (EBI), we are now close to complications and help recov- lenge from Dr Sanjoy Shah, seeing some real impact from ery, yet its potential has not Consultant in Intensive Care a prehabilitation intervention yet been sufficiently explored. Medicine at University Hospi- for cancer patients undergoing Researchers aim to improve tals Bristol NHS Foundation major surgery. The project, surgical outcomes in cancer Trust (UHB), to develop a which aims to identify inter- patients by boosting health in ‘prehabilitation’ programme ventions that improve post- the vital weeks before surgery. for patients having major can- operative recovery, has been Maria led collaborative re- cer surgery. awarded further funding to search to identify interven- take forward this important tions that improve post- research. operative recovery and de- crease the length of hospital Dr Maria Pufulete (Research stay. Such interventions may Fellow, Clinical Trials and Eval- include dietary, exercise, psy- uation Unit at the University of chological and physiological Bristol) has been awarded components. The team applied £1,854,558 from the National for an NIHR Health Technology Institute for Health Re- Assessment grant to test one search (NIHR) Technology As- prehabilitation intervention sessment Programme. The (inspiratory muscle training) project was part of the Eliza- that was shown to work by the beth Blackwell Institute's 'Re- systematic review. search for Health Chal- lenge' scheme. The project received its origi- nal funding from the EBI Re- Improving patients’ health and

@BristolCancer

The Cancer Research Network you could contribute to is delighted to announce it has curating the feed, please con- set up its first social media tact Catherine Brown. If you feed via Twitter, @Bristol- already have a Twitter account Cancer. This is an exciting op- please do follow us and re- portunity for PhD students, tweet at will! junior and/or senior staff to become more involved in de- veloping communication chan- nels with the wider Cancer community across the Univer- sity and externally. If you feel Page 11

ELIZABETH BLACKWELL FUNDING

EBI Identifying Candidates for Investigator Awards This scheme is designed to support a small number of permanent academic staff at UoB within the first five years of their appointment, who are planning to apply for an Investigator Award from the Wellcome Trust. Applications will be accepted on a rolling basis.

Heads of Schools are asked to nominate members of staff who can be eligible for this scheme by emailing [email protected]

EBI Workshops Funding Support interdisciplinary workshops in health research at new or emerging interface between two or more disciplines. Applications reviewed all year.

Returning Carers Scheme To support academic staff across all faculties in re-establishing their independent research ca- reers on return from extended leave (16 weeks or more) for reasons connected to caring (e.g. maternity leave, adoption leave, additional paternity leave, leave to care for a dependant.).

The deadline for applications is 30 April and 31 October each year.

EBI Bridging Funds for Senior Fellows This scheme is designed to support a small number of academic staff at the University of Bristol who currently hold an externally funded research fellowship. Applications accepted on a rolling basis.

Page 12 Cancer Network Newsletter

FUNDING OPPORTUNITIES

Would you like to receive timely, tailored funding opps information? Do you want to know what funding opportunities come up in your research area? Get tailored funding alerts?

Research Professional provides access to an extensive database of funding opportunities, and can send out tailored alerts based on keywords that you input, ensuring that the funding alerts you receive are the ones you want to hear about. UoB staff and students have FREE online access to the database from any device – once you’ve registered then you can view upcoming funding opportunities from home or away, not just while on the University network.

You can search for funding information by discipline, sponsor, database searches, by recent calls or by upcoming deadlines. If you register for the site and log in, you’ll be able to:

• Set up automated funding opportunity email alerts - tailored according to your discipline and research interests, an easy process that will take just a few minutes to set up through the use of keywords • Save searches and bookmarks - store items of interest for future reference, download and email to colleagues • Sign up for higher education news bulletins – want to hear about what is going on in the broader HE environment? Latest news on the REF, setting up of UKRI etc? Sign up for the 8am playbook or the Research Fortnight news publications and stay up to date with the latest news.

Alternatively, a full calendar of funding opportunities for neuroscience research has already been set up and is available online. Subscribing to the calendar will place the entries in your own calendar, which will automatically update according to pre-specified search criteria. Find out more about Re- search Professional on the RED website. Note that some calls may have an internal process; do always remember to check the major bids webpage here to see if there is an internal process.

The following listings represent a brief selection of available funding for the Cancer Research communi- ty. Full listings of opportunities are sent out via Faculty Research Directors and/or School Research Directors, and are available on the Research Development website.

Department of Health and Social Care Global health research programme – research and innovation for global health transformation

Closing date: 01-Aug-18 Award amount: £5m

This supports interdisciplinary applied global health research for the direct and primary benefit of pa- tients and the public in low- and middle-income countries. Research challenges in infection-related cancers are included in this call.

National Cancer Institute, USA Page 13

Inter-organelle communication in cancer (R01)

Closing date: 15-Aug-18 Award amount: USD275,000

This supports research projects that examine how inter-organelle communication in cancer cells and tumour-associated cells affects cellular function, adaptation and phenotypic plasticity.

Cancer Research UK Pioneer award

Closing date: 05-Sep-18 Award amount: £200,000

This supports high-risk, high-reward research projects that have a clear relevance to cancer, and ena- bles the exploration of novel ideas which may lead to new discoveries or approaches. Early-stage ideas from any discipline are welcomed.

Cancer Research UK Predoctoral research bursary

Closing date: 18-Sep-18 Award amount: £200,000

This allows clinicians and other health professionals to get involved in research projects early in their career. The bursary gives the applicant a greater understanding of research before deciding whether to undertake a PhD or MD, or gives the applicant the time and resources to obtain preliminary data be- fore applying for a PhD or MD.

Cancer Research UK Early detection programme awards

Closing date: 25-Sep-18 Award amount: £12.5m

These support long-term, integrated and renewable programmes of exceptional science to transform how and when early cancers and pre-cancerous states are detected. Projects may focus on any specific or combination of the following research areas: • biological research underpinning early detection and biomarker discovery and validation • human-based early detection discovery research • epidemiology and risk stratification for early detection, to inform populations for targeted re- search or screening • data and computation-driven approaches to early detection • development and utilisation of preclinical early detection model systems • early detection technology development • translational and clinical early detection research Page 14 Page 14 Cancer Network Newsletter FEATURED PUBLICATION

Biodegradable, Drug‐Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics Ridolfo R, Ede BC, Diamanti P, White PB, Perriman AW, van Hest JCM, Blair A & Williams DS

The stabilisation and transport of low‐solubility drugs, by encapsulation in nanoscopic delivery vec- tors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technolo- gies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is neces- sary to reconsider the entire process from copolymer synthesis through self‐assembly and function- alization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)‐block‐poly(trimethylene carbonate), synthesized via organocatalyzed ring‐opening polymeri- zation, undergo assembly into highly uniform, drug‐loaded micelles without the use of harmful sol- vents or the need for purification. The direct hydration methodology, employing oligo(ethylene gly- col) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug‐loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an ex- citing candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are gen- erated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).

Schematic outlining the direct hydration methodolo- gy for the production of discrete nanovectors. Codissolution of PEG–PTMC copolymer (chains coloured blue and orange, respective- ly) and drug (red) in OEG (green solvent phase) is followed by stirring with aqueous buffer to create pristine nanovectors in under 10 min, without use of harmful solvents. During direct hydration, as the two phases coalesce, copolymer and drug undergo rapid hydrophobic co‐assembly into micellar constructs. Cancer Network

CONTACTS

Network Co-Lead: Professor Paul Martin Professor of Cell Biology

Network Co-Lead: Dr Axel Walther Senior Lecturer and Research Lead, Bristol Haematology & Centre

Catherine Brown, Network Administrator

• Dr Sabine Hauert, Engineering Mathematics

• Dr Zoë Holland, RED Facilitator

The Cancer Research Network is led by a • Prof Richard Martin, Professor of Clinical Epidemiology Steering Group:

• Prof , Head of School of Cellular @BristolCancer and Molecular Medicine

[email protected] • Prof Caroline Relton, Professor of Epigenetic Epidemiology

bristol.ac.uk /cancer • Prof Ann Williams, Professor of Experimental Oncology 00 44 117 428 4012

• Dr Emma Vincent, Research Fellow and Early Career representative