As CRUK's Natalia Bartolome Diez put it, 'When done well, patient involvement can improve the quality and relevance of research, and is increasingly becoming a funding application requirement.' CRUK has asked researchers and people affected by cancer for their top tips on getting patient involvement right in all types and stages of research.
Here's a brief rundown of what they found:
1. Start early
The earlier you start planning patient involvement in your study, the more likely you are to involve the right people at the right time, using the most appropriate methods. Starting early helps you to gain deeper insights from the people you involve. It gives you time to embed their ideas in your research and make impactful changes as a result.
2. Take time to plan
The key to involving people affected by cancer meaningfully is planning. Taking time to think about the why, what, when and how of patient engagement will help you to identify key areas of your research that will benefit from patient involvement, and what this involvement should look like.
3. Involve the right people
You must find people affected by cancer who are able to give you the insight and information you need. Be clear about the requirements of the role and identify the skills, experience and personal attributes that the people participating in your activity will need to have.
4. Provide lay information
Explaining your study and general research topic to the people you are involving in your research will enable them to accurately feed into discussions. Information should be provided in clear, succinct, plain English. Don't assume that everyone you involve has the same abilities.
5. Establish ways of working
Ensuring that you and the people affected by cancer who become involved in your research feel comfortable and have positive experiences from the start is vital to encourage quality insight and feedback. It can be intimidating to enter a room full of researchers and muster the courage to dispute elements of their research or make suggestions. Therefore, the researchers and participants in involvement activities should agree on ways of working.
6. Don't reinvent the wheel
Make full use of the resources available from different charities, rather than trying to create a new way of doing patient involvement. CRUK can help you identify involvement opportunities at any stage of your research and support you in their delivery.
7. Always provide feedback
Many people affected by cancer start doing patient involvement because they want to 'give back' and improve outcomes for future patients with cancer. Patient involvement empowers them to influence change and provides a sense of purpose. For this reason, it is important that those involved are made aware of the impact and consequences their feedback and insight had on research.
The above is an abbreviated version of CRUK's Research Feature. Click here to read the full article.
In a pre-print available on BioRxiv ("RAL GTPases mediate EGFR/MAPK signalling-driven intestinal stem cell proliferation and tumorigenesis upstream of RAS activation"), Julia Cordero and Glasgow cancer scientists uncover a new role for Ras-like (RAL) protein in intestinal tumour growth. Beyond acting as a RAS effector, RAL stimulated the activation and internalisation of EGFR, a receptor commonly overexpressed in intestinal cancer. Hence, targeting RAL function could be an effective therapeutic approach.
Vassilis Papalazarou, Laura Machesky and colleagues describe how the Arp2/3 complex - a key factor in organising actin filaments into networks - not only has a role in the migration of melanoblasts but also in the development of skin and hair ("The Arp2/3 complex is critical for colonisation of the mouse skin by melanoblasts"). Upon depletion of the complex, melanoblasts didn't migrate properly in the developing skin, failing to populate it with hair follicles and pigment. Mechanistically, the authors suggest that melanoblasts form impaired lamellipodia and protrusions, which are essential for actin-driven migration.
Linda Rushworth, Rachana Patel, Hing Leung and colleagues identified TCEAL1 as a potential target to sensitise prostate cancer to docetaxel therapy ("In vivo CRISPR/Cas9 knockout screen: TCEAL1 silencing enhances docetaxel efficacy in prostate cancer"). Combining docetaxel treatment with TCEAL1 inhibition in culture impacted the regulation of the cell cycle and response to DNA damage. Further work is needed to investigate the effects in combination with standard care and to monitor the response in in vivo tumours.
From University of Glasgow press release (https://www.gla.ac.uk/news/headline_757602_en.html:
Dr David Bryant has been awarded £1.2m to undertake new research into colorectal carcinoma, beginning the OrgTIP project which will look at how inhibiting Phosphoinositide-modifying enzymes (PIP-MEs) could help to combat the disease. PIP-MEs are a family of genes that are commonly altered in many cancers, but particularly in bowel cancer. In bowel cancer, the PIP-MEs become uncontrolled to the extent they no longer work, or work when they shouldn't. The OrgTIP project will look at how to target the altered PIP-MEs without damaging normal cells.
Dr Bryant will also work with a biotechnology industry company partner to provide tools for the entire research community to develop new ways to combat cancer.
Dr Bryant said: "Bowel carcinoma is the 4th most common cancer in the UK, accounting for 1 out of 10 deaths from any type of cancer. While 6 out of 10 patients will respond well to current therapies, the rest will not respond to treatment. These non-responding patients have a very poor outlook and we therefore urgently need to develop new therapies to treat these patients. We hope targeting PIP-MEs may provide a new viable treatment option that may help those patients. "
The Medical Research Council (MRC) is investing more than £20m in a major new network in mouse genetics for disease modelling to accelerate our understanding of human disease and improve diagnosis and treatments. Here, Professor Owen Sansom, Director of the National Mouse Genetics Network, writes about his vision for the new network, the exciting opportunity for the UK, and plans to engage with the community.
Luke Tweedy, Robert Insall and colleagues at the Beatson report in Science ("Seeing around corners: Cells solve mazes and respond at a distance using attractant breakdown") that cells navigate complex environments such as man-made labyrinths by following and leaving chemical 'breadcrumbs', allowing pursuing cells to instantly find the shortest path and to avoid dead ends. This study helps us to understand how the environment and signals produced by other cells cue the direction of cancer spread.
Rob Wiesheu, Seth Coffelt and co-authors have made a pre-print available on BioRxiv ("Ly6C defines a subset of memory-like CD27+γδ T cells with inducible cancer-killing function"), which identifies a new subset of γδ T cells in mice that are similar to mature γδ T cells in humans. Culturing these cells stimulates their cancer-killing activity and opens up interesting opportunities for anti-cancer immunotherapy.
Chatrin Chatrin, Mads Gabrielsen, Danny Huang and Glasgow scientists describe a mechanism where ubiquitin itself becomes a target for post-translational modification ("Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases"). When binding NAD+, Deltex family E3 ligases facilitate the addition of ADP-ribose to ubiquitin (ADPr-Ub). This reversible process makes ubiquitin unavailable to the ubiquitin cascade and its associated regulatory machinery. The physiological role of ADPr-Ub, however, remains to be determined.
Together with their co-authors, Rafael Martinez and Hing Leung have distributed a preprint on BioRxiv ("Schlafen family member 5 (SLFN5) regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer") that provides large-scale analyses of proteins underlying three distinct castration-resistant prostate cancer models (CRPC). Although they identify distinct proteomic landscapes, SLFN5 is found at high levels in all models and is connected to poor outcome in patients. Mechanistically, SLFN5 changes the availability of metabolic building blocks in cells affecting a growth pathway underlying cancer.
Anna Koessinger, Dominik Koessinger, Jim Norman, and Stephen Tait together with other Glasgow cancer researchers ("Quantitative in vivo bioluminescence imaging of orthotopic patient derived glioblastoma xenografts") showcase a new technique to monitor long-term tumour growth in patient-derived glioblastoma models. Through imaging the overexpression of near-infrared fluorescent protein they have developed a method that is rapid, accurate and has clear advantages over conventional approaches.
Jacqueline Tait-Mulder, Alexei Vazquez together with Beatson Proteomics scientists link formate – its metabolism is increased in some cancer types – to the production of pyrimidine through the mTORC1 facilitated phosphorylation of CAD ("The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis"). How these events are linked to the tumour's higher demand for formate will need to be determined in future work
David Bryant and colleagues have shared a pre-print on BioRxiv ("Spatial enrichment of phosphoinositide metabolism is a molecular switch to promote metastasis") where they identify the protein IQSEC1 as a molecular mechanism to communicate to cancer cells whether to grow at the tumour site or become invasive and spread around the body. IQSEC1 directs the production of cellular messengers (phosphoinositides) to areas of the cells where forward stretching, invasive projections are formed. With the potential to reduce cancer spread, the inhibition of IQSEC1 makes an interesting target for potential therapeutic intervention.
CRUK Commercial Partnerships acts as the meeting point between the charity's funded research and industry. It helps to accelerate the translation of research into products for patient benefit through the development and commercialisation of exciting new discoveries. In addition, any revenue received through its commercial partnerships is reinvested back into developing lifesaving research.
This annual review aims to demonstrate the commitment of Commercial Partnerships over the last year to the researchers whom it supports with achieving their translational ambitions, the companies with whom it partners and the cancer patients to whom its efforts are ultimately dedicated.
Over the last financial year, Commercial Partnerships supported CRUK researchers to learn entrepreneurial skills, file 38 patents, create two spinout companies and re-invested £43 million back into cancer research. This includes scientists at the Beatson (page 23 of report).
Read the full report CRUK CP Annual Review 2019/20 (10.57 MB)