Prostate cancer : the right therapy for the right patient… but how ?
Dr. Fréféric Pouliot
Urologist-oncologist, CHU de Québec – Université Laval
Dr. Jean-Mathieu Beauregard
Nuclear medicine, CHU de Québec – Université Laval
Brigitte Guérin, PhD
Chair Jeanne and J.-Louis Lévesque of radiobiology, University of Sherbrooke
SCIENCE IN ITS WORDS / A diagnosis of prostate cancer, it is a bit like a sinister part of a coin. Stack, the cancer is indolent, and the patient can live with, even without treatment, and for a very long time. Face, the cancer is aggressive, does not respond to treatment (even if they are multiple and intense), and the patient dies in a few years. And all the variants between these two extremes are possible. Of course, doctors can differentiate between forms of cancers more aggressive lingering for advising the patient in his choice of therapy. But how is it that a same cancer behaves in so many different ways? And we, the oncologists, how is it that we can decide what to do when we are in front of an aggressive cancer ?
Although “cancer” is often used in a broad sense and in the singular to describe all cancers, it is now recognized that we should rather talk about “cancers”. First, the sensitivity of cancers to therapies varies according to the origin of cancer, i.e. according to the organ in which the cancer develops initially (breast cancer vs prostate cancer). It is thus necessary to adapt the treatment to the origin of the cancer.
Secondly, the behavior of cancers varies greatly from one individual to another according to the genetic is unique to each individual and according to environmental factors such as lifestyle habits.
Thirdly, it should be understood that in one and the same individual, the sensitivity of cancers to treatment changes over time : the cells change to become resistant to treatment and our immune system, a phenomenon called ” plasticity “. When it comes to cancers of the prostate, we know that there are sometimes several prostate cancers within a single individual with distinct responses to treatment. This is what is called the polyclonality and heterogeneity.
This greatly complicates the choice of doctors to decide on the best treatment to administer to a patient because the sensitivity of cancers to a particular treatment is difficult to predict. You can administer more than one treatment at the same time (e.g. : both hormone therapy and chemotherapy) in order to target a maximum of cancer cells but this is often at the cost of side effects increased. The ideal would be to know what treatment will work through biomarkers. The classical way to proceed is to take a piece of tissue cancers (a biopsy) to analyze it and to choose a therapy according to the characteristics of the tumor. But as the same patient may have several types of prostate cancer cells different, nothing says that the biopsy is representative of all cells. Thus, until recently, the biomarkers from biopsies have not been demonstrated to be sufficiently accurate to be used in the clinic.
It is therefore necessary to find a new approach which allows to evaluate all of the metastases at the same time and we are just part of a research team that is working on a new strategy against cancer : the “théranostique”. It combines the molecular imaging therapy “radioligand”, which uses radioactive molecules that are going to stick specifically to tumours.
Molecular imaging allows you to see specifically the metastasis of prostate cancers by injecting the patient with a radioactive tracer will attach to a protein highly expressed in these cancers, PSMA (Prostate Specific Membrane Antigen). Once linked to the PSMA, the radioactive tracer (or ligand PSMA) will emit photons that will be detected thanks to the technology available in the clinic, positron emission tomography (Figure 1). Of all the images of the patient’s body will then be generated.
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This allows to visualize more accurately the metastases, and can detect if they express the protein PSMA. Subsequently, the tracer is altered by techniques of chemistry so as to keep the part that attaches to the tumor (ligand) but replacing the “plot” by a molecule of radioactive very powerful (such as lutetium-177), which will be toxic to the tumor. Thus, the ligand will become a homing device that will bind to the protein PSMA from prostate cancer cells delivering specifically the lutécium radioactive nearby, such as a bomb on the metastases.
This type of therapy has proven to be very powerful to treat metastatic prostate cancer in clinical research. In patients treated previously by two or three hormone treatments or chemotherapy, more than half of the patients responded to the radioligand which is exceptional. In addition, pictures of each patient with the tracer PSMA before treating with the ligand, it is possible to know if all the metastases will be targeted by the ligands of PSMA in lutécium. In the case where some metastases do not express themselves not to the PSMA for the imaging, the patient could be shifted to other therapies.
In Quebec, we have started clinical studies using these approaches and we have treated several patients in the context of research protocols. Thanks to a collaboration of four universities (Université Laval, Université de Montréal, Université de Sherbrooke and McGill University, funded by the initiative Oncopole and the Merits of Health Research and Quebec), we are also developing new approaches to molecular imaging to better identify patients who are candidates for therapy to radioligand binding with the firm intention to offer these treatments on a larger scale in the near future for our patients.
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