Personalized, tailor-made, targeted: these are the attributes most used to define the “new” precision medicine, aimed at preventing or detecting as early as possible each disease and provide the most appropriate means to treat it according to the needs and characteristics of the patient.
How medicine has changed: from the population to the individual
Classical” medicine, in particular with regard to the research and application of new therapies, followed a more population-oriented approach, favouring the size of the average response in patients over the particular case, in order to assess the effectiveness of drugs in a statistically sound manner.
The approach of precision medicine, defined by Francis Collins, director of the National Institutes of Health, as “that set of prevention and treatment strategies that take into account individual variability” is different. It is a medicine that, by combining diagnostics and therapy in a hyper-specialized way, is able to recognize and “box” each patient in an individual and specific way, but always accompanying the technical accuracy of the medical act with attention to the patient in its entirety: in essence, with customization.
Technologies and new discoveries have paved the way for personalised medicine
The path towards precision medicine was undoubtedly started by scientific and technological revolutions: “the discovery of monoclonal antibodies played this role first and foremost” explained Professor Alberto Mantovani, Scientific Director of Humanitas and lecturer at Humanitas University. “This opened the way to the production of antibodies capable of recognizing a single small antigen, measuring its quantity, and even wanting to block its action, as needed. Not to mention the possibility of producing the desired antibody in unlimited quantities and with a standard quality, so that it can be used in the same way in all laboratories around the world. A discovery that has earned its authors the Nobel Prize for medicine and has rapidly revolutionized first the diagnosis and then the therapy. “It is enough to remember – noted Professor Mantovani – that the first targeted and precise therapy, capable of changing the natural history of a human tumour, was precisely a monoclonal antibody, rituximab. It works by blocking the CD20 marker (always detected by an antibody), specific for B lymphocytes that proliferate uncontrolled in various lymphomas and leukaemias”.
Genomics
A second, fundamental revolution has been that of genomics and of the technologies connected to it, which allow the analysis of the individual genetic patrimony. “These are technologies that in the last decade – explained Professor Gioacchino Natoli, professor at Humanitas University and researcher in the area of advanced genomic technologies – have seen enormous progress, including in terms of performance efficiency and cost reduction. So much so that completing the first sequencing of the human genome took over 10 years of work and about 3 billion dollars, while currently it takes only one day to sequencing several, with a unit cost of less than 1,000 dollars.
The patient’s genomic analysis makes it possible to quickly identify mutated genes in his DNA, which can be responsible for an ongoing disease and diagnostic for its recognition; or indicators of a predisposition, or rather of a greater probability, compared to another subject who is not a carrier of it, to develop a given pathology; or indicators of the probable evolution of that disease and therefore of the prognosis; or finally predictive markers, i.e. useful to predict a greater or lesser ability to respond to a specific therapeutic treatment.
Precision medicine and oncology
According to Professor Mantovani, “the paradigm of oncology has been and is the treadmill towards the realization of personalized medicine. This also has its own important specificity that perhaps makes it different from all other areas of disease – he explained – here, in fact, are the genetic characteristics of the cancer cell, and not those of the patient, to dictate in most cases the direction of the therapy. In oncology, precision medicine has already led to some therapies that are often decisive: in addition to rituximab, examples are the small imatinib molecule for chronic myeloid leukemia, all-trans retinoic acid, or ATRA, for promyelocytic leukemia, trastuzumab antibody for a type of breast cancer”. “We must seriously think about the concrete sustainability of a fascinating approach that is revealing how high its costs are – added the professor – And the question that looms, then, is not only if you are able to do precision medicine, but also if you can afford it, and to what extent, since for equity should be accessible to all,” concluded Mantovani.
Results and perspectives of precision medicine in oncology
“The development of technologies that make it less and less expensive to investigate the genetic code of a patient is fuelling a race to customize medicine, which began some time ago with molecular testing on neoplastic tissue,” said Dr. Luca Toschi, oncologist at the Cancer Center in Humanitas. “This can generate a substantial volume of data that contemporary medicine is gradually learning to use correctly. There are many positive aspects to this new approach that, especially in the oncology field, has already changed the standard of treatment of some diseases. The development of biological markers is a process that, although it may sometimes be complex, has already borne fruit, allowing the management of many new drugs to be optimized in terms of effectiveness and toxicity. Nevertheless, this approach is currently limited to only a minority fraction of patients. In fact, in most cases it is not possible to identify with certainty responders and non-responders with the markers available today, and this prevents us from being able to offer each individual patient a fully personalized therapy. However, a great deal of progress has been made, starting with imatinib and trastuzumab, the first targeted therapies developed that have triggered the race to develop specific drugs for the single ‘molecular’ variant of the disease”.
“To increase the number of patients who can benefit from precision medicine – added Toschi – it is necessary to train a new generation of doctors and researchers who can guide this transformation: it is essential to use the diagnostic technologies available to identify subgroups of patients, sometimes very limited in number, with specific therapeutic pathways and encourage the development of clinical studies in these populations. Consequently, in the era of precision medicine, an integrated multidisciplinary approach involving all specialists involved in the diagnostic and therapeutic process will be essential, with the aim of optimizing the personalization of the path of care. The task is complex, but we will be able to carry it out, provided that our young doctors achieve a strong scientific and clinical preparation,” concluded Toschi.
Asthma and personalised medicine
Also for bronchial asthma, in recent years antibodies have been developed with the aim of inactivating a precise mechanism causing the disease, especially for the most serious cases, resistant or not very sensitive to available therapies. “There is still a long way to go – said Professor Giorgio Walter Canonica, head of the Center for Personalized Medicine Asthma and Allergies in Humanitas and professor at Humanitas University – because unfortunately, for now, there is no evidence that would allow us to link the genetic characteristics of the patient to a specific mechanism, leading to a radical clinical change. In Humanitas” – added Canonica – we are studying, with first very interesting results, the possible use of enlarged panels, i.e. groups of markers rather than a single marker, to increase the ability to predict the response of the asthma patient to the different antibodies available for therapy”. In fact, the treatment has a high cost and, in addition to the necessary benefit for the patient, it is also important to make rational use of resources.
Results and perspectives of precision medicine in oncology
“The development of technologies that make it less and less expensive to investigate the genetic code of a patient is fuelling a race to customize medicine, which began some time ago with molecular testing on neoplastic tissue,” said Dr. Luca Toschi, oncologist at the Cancer Center in Humanitas. “This can generate a substantial volume of data that contemporary medicine is gradually learning to use correctly. There are many positive aspects to this new approach that, especially in the oncology field, has already changed the standard of treatment of some diseases. The development of biological markers is a process that, although it may sometimes be complex, has already borne fruit, allowing the management of many new drugs to be optimized in terms of effectiveness and toxicity. Nevertheless, this approach is currently limited to only a minority fraction of patients. In fact, in most cases it is not possible to identify with certainty responders and non-responders with the markers available today, and this prevents us from being able to offer each individual patient a fully personalized therapy. However, a great deal of progress has been made, starting with imatinib and trastuzumab, the first targeted therapies developed that have triggered the race to develop specific drugs for the single ‘molecular’ variant of the disease”.
“To increase the number of patients who can benefit from precision medicine – added Toschi – it is necessary to train a new generation of doctors and researchers who can guide this transformation: it is essential to use the diagnostic technologies available to identify subgroups of patients, sometimes very limited in number, with specific therapeutic pathways and encourage the development of clinical studies in these populations. Consequently, in the era of precision medicine, an integrated multidisciplinary approach involving all specialists involved in the diagnostic and therapeutic process will be essential, with the aim of optimizing the personalization of the path of care. The task is complex, but we will be able to carry it out, provided that our young doctors achieve a strong scientific and clinical preparation,” concluded Toschi.
Asthma and personalised medicine
Also for bronchial asthma, in recent years antibodies have been developed with the aim of inactivating a precise mechanism causing the disease, especially for the most serious cases, resistant or not very sensitive to available therapies. “There is still a long way to go – said Professor Giorgio Walter Canonica, head of the Center for Personalized Medicine Asthma and Allergies in Humanitas and professor at Humanitas University – because unfortunately, for now, there is no evidence that would allow us to link the genetic characteristics of the patient to a specific mechanism, leading to a radical clinical change. In Humanitas” – added Canonica – we are studying, with first very interesting results, the possible use of enlarged panels, i.e. groups of markers rather than a single marker, to increase the ability to predict the response of the asthma patient to the different antibodies available for therapy”. In fact, the treatment has a high cost and, in addition to the necessary benefit for the patient, it is also important to make rational use of resources.
