7 minute read
AT THE FOREFRONT OF ADVANCES IN CANCER TREATMENT
Dr Nick Plowman Clinical Oncologist
AT THE FOREFRONT OF ADVANCES IN CANCER TREATMENT
Everyone knows there have been advances in cancer, but most people are unaware of the truth behind the discoveries of recent years, from which cancer su erers will benefi t. Exceedingly few know the optimal order of various treatment options that are best for individual people. Indeed not all experts agree themselves! The baseline shifts.
What is clear is that there are now more cancer treatment options, and that all-important cancer prevention programmes are no longer confi ned to cervical screening, faecal blood testing and mammography, but are often based on genetic predisposition and ‘high-risk screening’ individuals (for example, low-dose CT on the lungs of heavy smokers) and even blood testing for circulating ‘cell-free’ mutated DNA fragments – a signature of cancer. For established cancer, the staging of the disease is paramount. Not only do we now have advanced anatomic imaging (notably CT/MR), but also functional imaging, notably PET scanning (often more sensitive for diagnosing the extent of the cancer) and where the individual characteristics of particular cancers can be used for specifi city (a good example being PSMA-PET scanning for prostate cancer).
In cancers that grow slowly over time and spread to distant sites (‘metastasise’) later in their natural history (eg cancers of the head and neck, such as larynx, mouth, pharynx), regional treatment for early cases – predominantly surgery and radiotherapy – is attended by high cure rates. Advances in surgery usually hit the press, but advances in radiotherapy are often overlooked. The introduction of charged particle beam radiotherapy ▸
(at present, protons in UK) is of great importance. This type of radiotherapy is important as it markedly reduces collateral damage in structures adjacent to the tumour. Although the UK has commissioned two cyclotronbased centres, London will see the introduction of linear acceleratorbased proton beam radiotherapy in 2021 – an advance in technology and dosimetric accuracy that may eventually supplant all other radiotherapy methods, and at significantly lower price.
For cancers that have spread to distant body sites or for higher-risk cases despite apparently being early-stage, patients have to be managed with therapy that reaches all body parts. These used to be chemotherapy, or anti-hormonal therapy for some breast and prostate cancers. However, immunotherapy and genomically targeted therapy, using drugs that block the abnormal protein/enzymes encoded by the mutated DNA, have added significantly to the impressive prolongation of life in those presenting with metastatic cancer.
Often there are predictive tests that can be carried out on tissue (biopsy) specimens from the cancer, which will allow the clinician to know the therapeutic potential of new drugs. Importantly, some of these mutations can be treated by ‘smart’ drugs that block the downstream transcription/ translation protein enzyme products of the DNA mutation – the driving oncogenic stimuli to the cancer cells to relentlessly go on dividing beyond the requirements of the body. This is called genomically targeted therapy prediction and has become very important in modern oncology.
In other words, by analysis (by nextgeneration sequencing – NGS) of the cancer’s genomic make up, we can select appropriate drug therapy (so-called ‘personalised cancer therapy’) for blocking the oncogenic stimuli generated by the mutations – the cause of the cancer.
‘Smart drugs’ are now in routine use and are highly eective in the therapy of lung, kidney, some breast and colon cancers, melanoma and an increasing number of other cancer types; indeed, the remissions accruing from their usage often exceed that by more conventional therapies. It is the genetic mutation that predicts their usefulness, rather than the tissue of origin of the cancer.
Sometimes analysis of the blood, where DNA fragments from dying cancer and normal cells circulate for a short halflife and the mutated DNA fragments ▸
A seamless pathway for prostate care Get quick diagnosis and tailored treatment for prostate cancer
Prostate cancer aects more men in the UK than any other cancer, but with quick diagnosis and tailored treatment there is a very good chance of beating it. Bupa Cromwell Hospital oers a quick, easy patient pathway, with leading urologists providing:
• Seamless transition from GP appointment or health assessment (if abnormal PSA detected) onto the pathway for diagnosis and treatment
• Experts in the field who guide you through each step
• Swift and accurate diagnosis, including quick test results
• Services accessible to all, whether using health insurance or self funding. Available to UK and international patients
Bupa Cromwell Hospital registered office 164-178 Cromwell Road, London SW5 0TU, United Kingdom. Bupa Cromwell Hospital Trading Companies: Medical Services International Limited, registered in England and Wales number 01416977 • Cromwell Health Group Limited, registered in England and Wales number 05687373. Call us on 020 7460 5700 or email appointments.team@cromwellhospital.com to discuss treatment details and book an appointment bupacromwellhospital.com/prostate
can be sorted from the normal by NGS and probed for the aforesaid mutations. Such a technique can also be used for monitoring the response of cancer by looking for the disappearance of such mutated DNA fragments from the blood.
Immunotherapy has been shown to enhance control rates when added to or sequenced with chemotherapy – eg for cancers of the head and neck, and lung cancer – that have spread/metastasised. The rationale of immunotherapy is also based on cancers being the product of mutations in DNA. Another consequence of this is that the abnormally coded proteins (consequent upon mutations) lead to new antigens (neo antigens) on the cell surfaces.
In foetal life, the developing immune system, which makes us reject transplanted kidneys from a stranger due to their foreign antigens, learns to ‘accept’ the dierent potential antigens on the body’s organs (a process known as ‘selftolerance’), so that there is no immune attack on them in later life. Occasionally, this self-tolerance goes wrong and the various autoimmune diseases, such as Hashimoto’s thyroiditis, result.
Conversely, and cancer is particularly adept at this, developing tumours express markers that interact with surface markers on the lymphocytes (and particularly their PD1 receptors) that mediate immune attack on such foreign tissues. This
confuses the immune attack by ‘fooling’ those lymphocytes that the tumour is actually a normal tissue for which there is self-tolerance. The present success of immunotherapy in cancer therapy is based on the ability of the new burgeoning line of drugs that ‘tear down’ that smokescreen and allow the immune system to see the neo antigens on the cancer and thereby lead to its rejection – just as it does to a transplanted kidney to a foreign donor (that is without added immunosuppression by the clinician). Immunotherapy, using PD1 and PDL1 inhibitors, is now mainstream therapy for lung cancer, melanoma, kidney cancer and some breast and colon cancers, with many other cancers being explored for susceptibility – once again, this susceptibility is primary tissue organ agnostic, implying broad utility.
How the new genomically targeted group of drugs and immunotherapy ‘interdigitate’ with chemotherapy, where they overlap and where they are most usefully used together, are all hot topics for trials at present. Recently, it has been shown that the addition of immunotherapy to lung cancer chemotherapy augments the response and, in kidney cancer, the combination of genomically targeted therapy with immunotherapy has become the prime first treatment for metastatic kidney cancer patients. Indeed, similar inroads are being made in uterine cancer with just such a combination. Soon, this combination approach will surely gain traction for other cancers.
Clearly, all this is important in choosing the correct first-line treatment for patients presenting with advanced cancer. There has also been a conceptual shift in the classification of cancers from, say, ‘lung’ cancer to one that classifies cancer by its genetic mutations (ie its genetic signature).
In London, multiple cancer units are looking at new optimisation of treatment schedules for patients with cancer. We are fortunate in the capital to have advanced cancer screening and many institutions with high-resolution scanning and staging procedures, easy availability of laboratory testing, front-line access to all genomics by NGS technology for tissue circulating free DNA and prediction for immunotherapy. Many advances in our subject are taking place in London, with world-class research and clinicians practicing these modern approaches in our city.
