Q: What are the results of precision medicine in your field of expertise?
Α: Precision medicine is a new dynamically evolving approach in medical therapeutics according to which therapeutic interventions are tailored according to the specific characteristics of the patient and/or his disease. In conventional medicine therapeutic decision is «speculated» on the basis of clinical and phenotypic characteristics, whereas, the goal of precision medicine is to distinguish between patients who could benefit from the treatment from those for whom the benefit is unlikely.
Medical oncology is an important field of application of precision medicine. Traditionally, treatment of patients with cancer was decided according to the tissue from which the tumor originates in conjunction with several markers mainly identified through further phenotypic analyses of the tumor. In recent years, however, Oncology has been increasingly focused on the molecular classification of tumors, as it provides the opportunity to administer drugs targeting specific genetic changes that are critical to the progression of cancer and thus to achieve rapid tumor shrinkage.
This new approach to cancer treatment was dramatically accelerated with the development of imatinib, which was approved for the treatment of chronic myelogenous leukemia in 2002. Indeed, imatinib, a small molecular inhibitor of the fusion kinase BCR – ABL1, the genetic change that drives the development of CML, is associated with impressive clinical results. Since then, the burst in the development of new technologies has enabled the discovery of the genetic make-up of tumors and it soon became apparent that molecular changes in genes related to DNA damage repair, cell division and cell death play a central role in the development of cancer. Moreover, it was understood that targeting these molecular changes can improve the survival of patients.
Genomic tumor analysis is now part of the established treatment of patients with lung adenocarcinoma. Specifically, testing is performed to detect specific mutations of the EGFR, BRAF genes and ALK and ROS rearrangements for which new biological agents that specifically target these changes are available. BRAF mutations are also determined to tailor treatment decisions in advanced melanoma, since BRAF inhibitors are also extremely effective for patients with BRAF positive tumors. In colorectal cancer the detection of mutations in BRAF and genes of the RAS family are also considered before treatment decision making. Finally, in breast cancer, treatment is traditionally determined on the basis of the expression of estrogen and progesterone receptors, the Ki67 proliferation marker and the amplification or overexpression of the HER2 receptor. In recent years, however, several gene signatures predicting the risk of relapse are used for therapeutic decision making in early breast cancer, whereas, more recently, the detection of mutations in BRCA1/ BRCA2 genes allows the administration of PARP inhibitors, a new class of drugs, with impressive treatment results in this specific subset of patients.
Immunotherapy is a new revolutionary cancer treatment aiming in the alleviation of the inhibition of T cell immune response against the tumor. Immunotherapy in the form of immune checkpoint inhibitors has transformed the care of patients with lung, head, neck, kidney, urothelial cancer and melanoma. Through the achievements of precision medicine, immunotherapy can be administered regardless of the histology of the underlying malignancy, in patients whose tumors have microsatellite instability, a molecular change associated with impaired DNA damage repair.
Q: What is the impact of the application of precision medicine in human health in the future?
Α: For the time being the advances of precision medicine in oncology can be applied only to specific subgroups of patients with cancer. For these patients precision medicine already offers significant advantages over classical chemotherapy and many believe that in the next few years it will become the standard approach when treating cancer patients. The genomic analysis of tumors has revealed that there are significant differences in the genetic composition of tumors among different patients but also that the tumor of the individual patient is a collection of different molecular abnormalities, a phenomenon called intratumoral heterogeneity. This heterogeneity is responsible for the emergence of cancer cell clones presenting resistance to novel anti-cancer agents. Targeting of the specific genetic changes of these resistant clones is a crucial measure towards successful tumor eradication. The analysis of «liquid biopsy», the genetic material that originates from various parts of the tumor and circulates in the blood of patients with cancer, promises to offer insights in intratumoral heterogeneity and to uncover genetic alterations which upon specific targeting could reverse resistance to treatment.
When facing cancer, prevention is of utmost importance. It is well known that about 40-50% of cancers could be avoided through prevention. Particular genetic differences among individuals in conjunction with environmental and lifestyle factors are responsible for the vulnerability to cancer. The analysis of these genetic differences could provide specific insights into the etiology of cancer as well as biomarkers for its early detection. These changes could distinguish the population according to the risk of developing cancer for the implementation of properly adapted screening strategies.
Finally, beyond Oncology, precision medicine sets the standards for research into other fields of medicine such as in cardiac and inflammatory diseases, infection diseases and diabetes. It is anticipated that precision medicine will provide novel insights into the etiology, will provide novel therapeutic interventions as well as adjusted preventive measures for a wide spectrum of human health problems.
First Ladies S. Aggelaki
