A new approach to cancer treatment is a personalized protocol, tailored individually for each patient.
Dr. Raanan Berger – Director of Oncology Institute, Chaim Shiba Medical Center, Tel ha Shomer, Israel.
Personalized treatment is a new approach that supposed to be a future for cancer management.
Why personalized treatment is important?
Two women with breast cancer and metastases in the lungs come in oncology department. Both women have tumor of 2 cm in the breast and 4 lung metastases, the same pathology response, both patients receive the same treatment protocol. One patient responds well to treatment – the tumors disappear, but the woman suffers very much from the toxicity of therapy – nausea, vomiting, oppression of bone marrow functions, fever and severe weakness.
The second patient has a completely different picture: she does not suffer from toxicity, except for a small decrease in blood counts, but at the same time, existing ones increase and new metastases appear in the liver. The life span of the first patient is increased by several years, while the second woman dies within a year.
This is a typical example, which is part of the everyday reality of the Oncology Institute. Two patients, equally diagnosed, may react differently to the same drug. To one treatment helps, while others may experience undesirable side effects without a therapeutic effect. This is partly because of different genetics (DNA) and other biological differences between people.
The idea of personalized medical care is to use the knowledge of these differences accumulated to date in the development of medicines, so that they are directed at each unique population of patients.
Until now, cancer treatment by chemotherapy and radiotherapy was based on the results of empirical studies that proved the statistical correspondence of the effectiveness of treatment of a particular disease. However, the results of the studies are not able to predict the response of a certain patient who suffers from a specific tumor, under the same treatment. Consequently, now much effort is focused on clinical and laboratory research to develop laboratory tests that will help in assessing the risk, early detection and identification of personal anti-cancer therapy for each patient, taking into account its individual characteristics, to fight a specific type of cancer.
Personalized medicine was established to help a physician make decisions for patients treatment at three levels:
1. Tests for diagnosis of the presence of genetic / hereditary syndromes – tests that focus on the relationship between the patient and his disease, and mainly genetic tests to assess susceptibility to malignant diseases. This is the goal of preventing the disease, in cases of detection of an innate genetic modification in a person’s genetic material.
2. Pharmacogenetic tests are tests that focus on the patient’s reaction to the drug. These genetic tests are designed to assess the nature of the patient’s metabolism when exposed to various drugs, in order to predict the degree of positive or negative effects that a specific drug may have on an individual.
3. Genomics tests focus on the relationship between disease and treatment. They are performed for predicting the course and effectiveness / resistance to treatment, by studying the genetic profile of tumor cells.
Pharmacogenetics.
In order to achieve the effect of an anti-cancer drug, the dose of chemotherapy should be optimal. Treatment, as a rule, is given in doses that cause toxicity. There is a large variability among patients regarding the effect of treatment.
Pharmacogenetics shows the genetic changes associated with the metabolism of the drug in the human body. Pharmacogenetics provides molecular data for fine tuning of chemotherapy personalization, allows to reduce toxicity and increase the effect. Genetic diversity (embryonic polymorphism) leads to a change in the activity of enzymes that affect metabolism, carrier or purpose of pharmaceutical drugs. However, modern treatment programs practically do not coincide with the genetic components of the patient. Therefore, personalized medicine is very important in the selection of a really working medicine for each person and his case.
Biological and chemical preparations.
Molecular targets in malignant cells, the identification of mutating genes and changes that begin with the transmission of an intracell signal associated with malignant transformation show that there is a “signature” of genetic aggressive tumors. This leads to the development of targeted biological agents (targeted therapy).
It should be noted that along with such advanced biological preparations, there are also chemical preparations whose work is directed at specific cell targets. The main difference between biological and chemical preparations is that biological preparations track the inhibitory genes or proteins with a change (mutations, deficiency, division) that exist in cancer cells and do not touch healthy cells. Thus, biological preparations have a wider therapeutic effect due to their ability to significantly differentiate malignant cells and cells of healthy tissues.
Accordingly, in the context of the use of biological and chemical drugs, before using them, it is important to study the “goals” of the proposed treatment. Characteristic presence / absence / change of these cellular targets allows to predict the effectiveness / inefficiency of drugs used in general and, in particular, biological preparations.
Tests performed for personalized medicine.
During the treatment of breast cancer and colon cancer diagnosed in the early stages and after local surgical treatment, oncologist faces the need for systemic therapy, chemo- and / or biological, for the prevention of relapse (adjuvant therapy). A few years ago, the oncologist relied only on clinical and pathological parameters, such as patient’s age, tumor size, stage and the like. In the last decade, genomic profiles have been identified (testing tumor gene expression), which allows the oncologist to accurately predict the risk of recurrence, and, accordingly, draw conclusions about the balance of benefits and risks when treating a patient.
Breast cancer test. Many women diagnosed with early stage breast cancer are treated with chemotherapy to prevent relapse, but most of them have no effect. The oncotype test accurately predicts the risk of recurrence in women who have been diagnosed with breast cancer at an early stage and whose tumor shows expression to the hormone receptors (estrogen and progesterone).
This test allows the doctor to determine competently whether the prognosis will improve the additional chemotherapy, or patient can be treated with hormone therapy. During the test, the expression of 21 genes in the tissue of the removed tumor is measured. The test result is given as a number between 0 and 100, to assess the risk of relapse. This test can significantly affect the determination of the type of medication and its consequences. When a patient can avoid treatment with chemotherapy, this is already a significant contribution to the quality of his life. At the same time, when the test indicates the need to treat a patient with chemotherapy, it saves a person’s life.
Oncotype test Colon Cancer. Prognostic genomic test of recurrence risk of colorectal cancer in patients who had colon cancer at an early stage (stage 2). This test is similar to the breast cancer test, it helps doctor decide on the need for a preventive course of chemotherapy after surgery. During the test, the expression of 12 genes in the tissue of the removed tumor is measured.
Test Target Now. This test helps in choosing the most effective therapy, based on the molecular profile of tumor cells. The test is intended for patients diagnosed with solid tumors that progressed during the first line of treatment and whose disease does not respond to conventional drugs. The test analyzes the genetic profile of tumor cells, scans a large number of potential targets for the action of the drug and provides a list of drugs that are known for their effectiveness against these targets. In many cases, the results show therapeutic possibilities that were not included in the original principles of treatment, which often excludes the possibility of using a drug suitable for the treatment of the disease.
Enhancement of genetic decoding of unknown origin miRview MET. There are cases when patients develop metastases, and the origin of the tumor is unknown. In such situations it is difficult to choose an effective treatment. A new genetic test, called MiRview Mets, is a breakthrough in the treatment of such patients. The test is performed on metastases, and can identify the source and organ from which the primary tumor and metastases spread. In the test, a sample of tissue metastasis is used, whose molecular profile is compared with the existing database of molecular profiles of tumors of various types. Thanks to this test, doctors can determine the type of cancer and prescribe the exact treatment for the patient, thereby increasing the chances of his recovery.
The latest innovations.
Sequencing the genome is one of the directions of personalized medicine for cancer patients. This is an area where the future becomes a reality on a daily basis, and personalized medicine develops in the process of diagnostic tests at a rate that sets the pace for scientific discoveries in the field.
Sequencing the genome is one of the directions of personalized medicine for cancer patients. This is an area where the future becomes a reality on a daily basis, and personalized medicine develops in the process of diagnostic tests at a rate that sets the pace for scientific discoveries in the field of cancer research. After the completion of the human genome project, several laboratories around the world began to invest in the joint efforts of the cancer genome project. This project uses information to identify gene mutations associated with malignant transformation directly from about 350 genes known to us today, up to about 2000 genes, in the foreseeable future.
The complete mapping of all melanoma somatic tissue mutations published in the scientific journal Nature in 2010, makes it possible to distinguish somatic mutations that play a role in initiating the cancer process (also called mutations, drivers), and mutations associated with them, and which are significant in malignant transformation of tumor cells (passenger mutations). In the same year, a full review of somatic mutations in small cell lung cancer cells was published in the journal Nature. Containing information on the characteristics and differences of mutations due to the effects of nicotine and other mutations.
Already today there is no doubt that with the discovery of complete mutation processes of specific cultures, a very large “target bank” will be created, and this will promote the development of targeted drugs for certain diseases. At the same time, these specialized tests can predict how effective the expectation of using the drug, regardless of the type of tumor, and based on the mutation profile of the tumor. In addition, it will be possible to obtain a good and accurate characterization of the patient’s treatment prognosis.
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