By Miranda Payne
Oncologists have long known that one patient is not the same as another. Indeed one patient’s cancer is not the same as another’s. Regardless of apparent clinical similarities, doctors witness huge variations in rates of cancer progression and patients’ response to treatment. There is increasing understanding of the need to investigate the multiple molecular differences between cancers, which may predict differences in patterns of growth and spread, and assist in the selection of the most effective treatments, whilst avoiding treatment in those unlikely to benefit. These molecular differences can evolve during the course of a patient’s disease, so that the cancer from which a patient might die may be very different to the one with which they were originally diagnosed. Exciting as these advances are, they bring into stark relief just how difficult the challenges faced by the patient and their oncologist are: how to develop treatments to which the individual’s particular cancer is likely to respond, and how to mount a re-challenge should it evolve.
In recent years, cancer immunotherapy has returned to the forefront of cancer research. This aims to exploit the power and targeted response of the patient’s own immune system to fight their cancer. Resurgence in interest has been prompted particularly by developments in the management of malignant melanoma, a type of skin cancer as well as kidney cancers, along with exciting clinical trial data in patients with lung cancer. Many patients with a diagnosis of secondary melanoma now routinely have access to the anti-cancer treatment ipilimumab, an antibody which triggers a specific response from a sub-group of the patient’s own white blood cells (called cytotoxic T-cells). One role of these T-cells is to recognise and kill cancerous cells, but to protect the rest of the body from unnecessary attack, this response is usually dampened down. Ipilimumab ‘releases the brakes’ from the immune system, speeding up the reaction time and growth of the T-cells. For a small minority of patients with secondary melanoma this can result in control of their tumour, sometimes lasting years, offering a tantalising insight into the potential of the immune system to eliminate cancerous cells. But the majority of patients derive no benefit, yet may suffer the multi-organ side-effects of the drug and the average survival with secondary melanoma continues to be measured in months.
How then to provoke the immune system more consistently and more specifically? Following successes with vaccinations against infectious diseases, there has been inevitable long-standing interest in the concept of vaccination to provoke a useful reaction against established cancers. Despite numerous avenues of research, little has translated into clinical practice. A solitary ‘therapeutic cancer vaccine’ currently approved by the US Food and Drug Administration for use in asymptomatic patients with hormone-resistant secondary prostate cancer has yet to find its place in the routine management of this disease.
Particular recent research focus has been on the role of the dendritic cell within the immune system, a cell derived from the bone marrow which captures ‘foreign’ material and is highly efficient at presenting it to T-cells, effectively launching the immune system to target the ‘foreign’ material. Earlier this year the BBC reported on a clinical trial underway in patients with glioblastoma, a brain tumour typically with a dismal prognosis and a low chance of responding to standard treatment options. There are over ten published small-scale studies performed along similar lines which, collectively, hint sufficiently at improved outcomes to justify expanding recruitment to several hundred patients. A sample of each patient’s tumour has been mixed with a sample of their own dendritic cells, before re-injection at intervals over a two year period. Each patient’s injection is a unique blend of their own cancer and their own immune cells, reintroduced to their immune system in the hope of educating it both to recognize their cancer as a target for destruction — and to remember that cancer, should it re-emerge in the future.
Results of this individualised cancer vaccine in patients with brain tumours are awaited, but the drive for evidence-based personalised cancer therapy has already advanced routine oncology practice. For instance, a patient’s breast cancer can be risk-stratified by analysis of a panel of mainly cancer-related genes. This can help the patient decide with their oncologist whether chemotherapy is the right treatment for them.
Future years will see rapid expansion in the concept of personalised cancer care, likely to encompass all aspects of the patient’s pathway, from diagnosis to treatment. The latest emerging concept is the ‘Mouse Avatar’ – the implanting of a sample of a patient’s cancer into an immunodeficient mouse to provide a personalized, living and reproducing model of that patient’s unique cancer. In theory this could enable oncologists to offer treatment to patients for which there is evidence of response in ‘their’ mouse. In reality, this technology remains in the earliest stages of development and multiple hurdles can be anticipated; scientific, financial and even ethical. Huge leaps are required before there is any prospect of it becoming a reality for the vast numbers of cancer patients requiring treatment each year.
But we have begun the journey towards the goal of personalised cancer care. Just as doctors should endeavour to treat each patient as unique, it seems possible that one day oncologists may be able to treat each patient’s cancer as unique too.
Miranda Payne is a Locum Consultant in Medical Oncology at the Oxford University Hospitals NHS Trust, specializing in the treatment of malignant melanoma, gynaecological and breast cancers. She took a first in Physiological Sciences at Oxford University and obtained her DPhil in Medical Oncology from Oxford University in 2010. Along with Jim Cassidy, Donald Bissett, and Roy Spence, she has been editor of the Oxford Handbook of Oncology for ten years and more recently, the Oxford American Handbook of Oncology (with Gary Lyman).