Targeted therapy
Personalized approach to cancer treatment
Justin Stebbing, Post-Science
The essence of the personalized approach in medicine is that we treat the treatment of patients not as a conveyor production, but treat them according to their individual needs. This means that we treat specific people with a specific cancer at the right time with the right methods.
Personalized treatment regimen for diseases
What does it mean to "treat specific people"? This means that everything depends on various individual factors: what are the patient's preferences, whether he wants to recover or not, whether he is young or not, in good physical shape or not, where he lives, what social circumstances he has, what his genes could affect the occurrence of cancer…
"At the right time" means that we try to diagnose cancer at the earliest stages. For this purpose, blood tests and various imaging methods are used. I am often asked: is it possible to cure cancer? Most cancers can be cured if they are diagnosed at an early stage, but if the cancer has metastasized, then we no longer consider it curable, even if we are talking about common cancers such as colon cancer, breast cancer, prostate cancer or lung cancer. In these cases, we strive to provide patients with the maximum life expectancy without losing its quality.
"The right methods" mean different things to different people. I adhere to an interdisciplinary approach, when decisions are made jointly by pathologists, radiologists, surgeons, as well as specialists working with medical treatments. We are trying to understand whether hormone therapy, chemotherapy, immunotherapy, radiotherapy or surgical intervention should be used in each specific case, when they should be used and in what order. When we organize interdisciplinary work and understand all these subtleties in a team, we will be able to treat patients better. But patients should also help themselves: stick to a proper diet, maintain good physical shape, and not lose optimism and motivation.
Targeted therapy and chemotherapy
If a tumor grows, we need to control cancer cells, and understanding the signaling pathways in cells and targeted therapy helps us in this. Targeted therapy allows you to target cancer cell proteins that are produced as a result of mutant or fused genes: drugs bind to these proteins, which are characteristic only of cancer cells, and do not affect normal cells. As a result, there are much fewer side effects, although they still happen from time to time. Thus, targeted therapy drugs are small molecules or antibodies that focus only on altered genes inside cancer cells. They work much more selectively and more effectively than other methods, but they are not suitable for all patients: you need to analyze cancer cells to understand whether the drug is suitable for this particular patient.
But sometimes there is no targeted therapy for this type of tumor, or it is not available (for example, due to the high cost), or we know that some genes are working incorrectly, and we used targeted therapy for treatment, but for some reason it stopped working. Then we need to use other approaches, such as chemotherapy, which still works despite the side effects: suppression of bone marrow activity, fatigue, hair loss or ulcers in the oral cavity.
One of the problems with chemotherapy is that it can kill all rapidly dividing cells, that is, not only cancer cells, but also hair cells, nail cells, intestinal cells or skin cells, and therefore it has so many side effects. For example, bone marrow cells divide rapidly to produce red blood cells and white blood cells – because of this, chemotherapy can lead to anemia or neutropenia. Due to the destruction of white blood cells, the risk of infectious diseases increases.
Nevertheless, chemotherapy still works, which some people forget. But when it comes to a personalized approach to treatment, they usually mean targeted molecular therapy based on our understanding of the work of genes both in normally functioning cells of different organs and in cancer cells. It is here that the main breakthroughs have taken place, are taking place and will continue to take place.
How to improve the effectiveness of cancer treatment?
When we consider a patient, for example, with breast cancer, the probability of her recovery increases due to not just chemotherapy or successful surgery, but successful surgery, chemotherapy, radiotherapy, hormone therapy, targeted therapy, and in some cases even immunotherapy for triple negative breast cancer. Having studied the genes of such a patient's cancer cells and having understood which genes in her normal cells could lead to cancer, we can personalize her treatment regimen, so that only she will undergo such treatment in my clinic – these therapies are in this order.
We discuss the possibilities of treating such patients at large meetings, fully dedicated to improving the outcome of the disease of each of our patients. By better understanding the different types of tumors, we will be able to better personalize the treatment regimen. Now we do not succeed in all cases, but we hope that in 5-10 years we will be able to guarantee that each patient with oncology will be treated according to an individual scheme developed specifically for his type of tumor in order to improve the duration and quality of their life.
The idea of introducing a personalized approach to cancer therapy does not belong to anyone in particular. It is rather a movement that arose when we realized that it was impossible to treat everyone the same. The template approach does not work. So, if you go to a shoe store, you will not buy a pair of shoes that someone else bought: you need exactly the shoes that fit the size and shape of your foot. Another example is a key and a lock: to open a specific lock, you need a specific key. The use of a personalized approach to treatment, targeted therapy, precision medicine – many people have started talking about all these ideas over the past few years. All these terms now mean that we will treat patients using molecular targeted approaches. As a clinical scientist, I am absolutely sure that this is the best way to increase the recovery rate of our patients.
My research in the field of targeted therapy is related to the genes encoding kinases inside cancer cells. Kinases turn on cancer cells, so we study cells of different types of cancer and look for ways to suppress kinases, turn them off. Most of the drugs for the treatment of cancer turn off the genes that are activated in cancer cells: if we better understand the work of these genes, we can make treatment more accurate, targeted and individual. Then we will be able to treat people better so that they live longer.
Future directions of research in this area are to understand at different levels how cancer cells change over time. If we understand how cancer stem cells and their network effects work, if we understand how the survival of cancer cells is affected by the dysregulation of not only cancer gene function, but also the gene function of connective tissue in the tumor, blood vessels, stroma and microenvironment, we can understand how best to disable the necessary genes to increase the level of recovery.
About the author: Justin Stebbing is Professor of Medicine and Oncology, King's College London.
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