The considerable improvements in the prognosis for patients with advanced disease in the past 20 years has been led by breakthroughs in our understanding of the molecular drivers of cancer. This understanding has fuelled the development of therapies that target cell signalling, angiogenesis and the host immune response.
Cell signalling: Many cancers are driven by genetic mutations that upregulate molecular signalling pathways promoting survival and proliferation; by blocking these pathways, therapies have been developed that can disrupt this process.
In breast cancer, Herceptin (trastuzumab) was the first monoclonal antibody to target a specific cell receptor, in this case HER2, overexpression of which had until then been a marker of particularly poor prognosis. Similarly, the management of chronic myeloid leukaemia was transformed by Glivec (imatinib), which was the first kinase inhibitor to be licensed in cancer and paved the way for a whole class of small molecules targeting different parts of the cell-signalling cascade in different cancer types.
Angiogenesis: Without their own blood supply tumours cannot grow larger than a pinhead, but many tumours are able to recruit cells involved in blood-vessel development to create their own vasculature.
The key to this process is vascular endothelial growth factor (VEGF) and its receptors, which are the target for a number of therapies, such as Avastin (bevacizumab) and Sutent (sunitinib).
The host immune response: Usually, the body’s own immune system destroys mutated cells, but cancers are able to avoid this process by signalling to immune cells to switch off.
For many years, there was a hope that it would be possible to harness the immune system to treat cancer, but with little success until the recent development of immune checkpoint inhibitors – therapies that control communication between tumour and immune cells or that stimulate immune response essentially, by removing the ‘brakes’ applied by the cancer on the immune cell.
This approach has been particularly effective in melanoma, where Yervoy (ipilimumab) and Opdivo (nivolumab) have set new standards, and it is also being applied in many other types of cancer.
These targeted therapies have changed the treatment landscape for patients with advanced cancer, in many cases offering the possibility of several lines of active therapy, with each new development extending survival beyond the boundaries ever dreamt of 20 years ago. Nonetheless, except in rare cases, they cannot completely eradicate the tumour, which will sooner or later develop resistance, requiring a new treatment approach.
Tumour resistance is a reflection of both heterogeneity between cells within a tumour mass and the availability of redundant signalling pathways within cells, which can come into action when the main survival pathway is blocked by a targeted therapy. The challenge, therefore, and the ultimate goal of cancer research, is to understand the individual network of factors that may contribute to tumour survival in each patient in order to offer a tailored treatment approach to maximise antitumour activity.
At the same time, adverse events need to be minimised to mitigate any impact on the patient’s quality of life. Although targeted therapies have been designed to have tumour-specific effects, they can still be associated with many side effects, often affecting the skin, gastrointestinal tract, blood vessels, and other organs. Such toxicities can substantially restrict a patient’s daily work and leisure activities, while even mild symptoms, if persistent, can have a big impact on the patient’s overall health and energy levels. These toxicities may necessitate treatment interruptions or dose reductions, potentially reducing the effectiveness of the treatment, or may even result in the patient stopping treatment altogether.
Meeting these combined needs of optimising antitumour activity and minimising adverse events requires multidisciplinary collaboration between research, oncology, pathology, radiology, surgery and the pharmaceutical industry, with all stakeholders keeping the patient at the centre of their focus. Collaboration between and within research groups and industry will maximise resource use and help focus activities on areas that are most likely to have a practice-changing effect.
The first step is diagnostic assays that can identify tumours most likely to respond to specific treatments. These assays need to be reliable and consistent (that is to say, sensitive and specific), use accessible technology that has rapid turnaround times, and be minimally invasive, e.g. by using ‘liquid biopsies’ (i.e. based on circulating tumour cells or DNA fragments in blood samples), rather than traditional invasive biopsy to remove tissue from the tumour itself. Liquid biopsies can be repeated more frequently than tumour biopsy, improving assessment of treatment response and disease progression.
Coupled with increasingly accessible next-generation sequencing, liquid biopsies can provide a more comprehensive picture of tumour heterogeneity and allow multiple mutations to be identified in one go. The ultimate goal is a point-of-care device that can be used in the oncologist’s office for on-the-spot tumour analysis and treatment planning.
Another major focus is optimal combinations of different targeted therapies, or targeted therapies and other treatment approaches (chemotherapy, surgery or radiotherapy) to minimise or overcome resistance. By targeting a range of molecular drivers at once and blocking redundant pathways, combination therapy can restrict the survival of clonal populations that are not dependent on any one particular pathway.
Most recently, the finding that some tumours are more likely to respond to immuno-oncology than others has prompted research into how to turn immunologically ‘cold’ tumours, which lack T-cell infiltration, into ‘hot’ ones, for example using bispecific antibodies that target receptors on both the tumour and immune cells or chimeric antigen receptor (CAR) T cells.
Finally, focusing on the whole patient rather than just the cancer in order to help them live well, with and beyond cancer, has emphasised the importance of recognising the adverse-event profile of each treatment in order to pre-empt and manage toxicities before they become treatment limiting. Crucial to this approach is good patient communication and education, enabling them to recognise and appropriately respond to adverse events and be an informed participant in their own treatment decisions.
More than 2,200 abstracts were selected for presentation at ASCO 2020 alone, illustrating the scale of the challenge faced by those trying to keep up with the latest developments.
With the COVID-19 pandemic prompting a surge in virtual interactions, the options for communication have now expanded exponentially, increasing the number of ways in which data can be shared with the aim that at least one route will reach the relevant audience (akin to the redundant pathways used by tumour cells described above). However, the flipside of this approach is that there is now more ‘noise’ than ever, making it harder for healthcare professionals to find the information that they need.
Face-to-face meetings will always have a central place in medical communications. Most healthcare professionals still agree that such meetings are one of their main ways of networking with colleagues, learning from experts and staying up to date. What is important is that these meetings offer a broad range of education, ideally across disciplines to foster multidisciplinary collaboration and provide most benefit for hard-working professionals who are increasingly restricted in how much time they can commit to professional development.
Peer-reviewed primary publications are the most widely accepted standard of evidence that forms the basis of treatment decisions. For the benefit of the whole research community, it is crucial that the results of all research, whether positive or negative, is made public to minimise unnecessary duplication of effort and increase the overall knowledge pool. Nonetheless, this approach does increase the amount of literature available and the time required to assimilate it. To aid readers, many journals now offer multimedia supporting information, such as graphical or video abstracts, which can help to highlight the clinical relevance of research.
At a time of unprecedented advances in oncology, it is crucial that research findings are accessible to and actually accessed by all stakeholders. It is only then that we can hope to evolve clinical practice and improve patient outcomes. To do this there are many communication vehicles available – from traditional publications to face-to-face meetings to online platforms, and all have their place in the communications mix.
Clearly, as suggested by this year’s digital-only ASCO meeting, online channels are likely to punch above their weight in 2020 and the COVID-19 crisis has provided valuable learnings about the best way to use virtual and digital communications. The coronavirus pandemic has certainly forced healthcare professionals and the wider population to rapidly upskill themselves about digital communications technologies.
The rate of change in oncology today can be bewildering, so it is imperative that the pharmaceutical industry supports healthcare professionals and that everyone works together to explore the most clinically relevant lines of research and ensures that knowledge is effectively shared in order to change the management of people with cancer for the better.
Sara Black is a principal medical writer at OPEN Health Medical Communications. With nearly 30 years’ experience in scientific publishing and medical education, she has a wealth of expertise in medical communications, particularly in oncology, and is an ISMPP Certified Medical Publications Professional
Christine Drewienkiewicz is a scientific services director at OPEN Health Medical Communications. Christine has over 28 years’ of experience in medical communications, scientific strategy and publishing, working across multiple therapy areas including oncology.
Annie Rankin is a strategic partnerships director at OPEN Health Medical Communications. Annie has worked exclusively in healthcare communications for over 10 years partnering with our medical affairs clients to drive meaningful outcomes against their strategic needs.
OPEN Health is a family of expert practices working in partnership to drive positive change in healthcare communications and market access globally. It all started with a vision for improving the lives of patients, worldwide. The OPEN Health vision has manifested with the integration of experts from Pharmerit and Peloton Advantage to create a new unique entity equipped to be a global leader in HEOR, market access, medical and patient brand communications and digital services.
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