The most precise treatments with genetic tests
Molecular genetic testing identified the most precise treatments
Genetic testing not only provides information regarding the chance of developing a particular disease but is also crucial in identifying the most effective anti-cancer therapy for each individual patient suffering from any solid tumour. Thus the battle against the tumour is tailored.
Genetic tests are basically of two types: the first is the predictive one, which allows asymptomatic people to reveal all the hidden secrets of their DNA and to quantify their risks of falling ill with certain diseases, cancer in particular, especially tumours of breast and ovary, colorectal and prostate and other diseases such as juvenile Alzheimer’s and cardiovascular diseases. The second type of test is aimed at people already suffering from cancer, a precision cancer test that is able to identify the most effective cancer therapy, especially biological, for each individual patient suffering from any solid tumour. From the routine paraffin blocks containing the excised or biopsied tumour tissues of the individual patient, stored in the pathology archive of the treating hospital, a piece of this material is sent to the precision oncology laboratory, for example Oncologica UK, based in Cambridge, UK. Here the sample is analysed using the Oncofocus test and within 10 – 15 days the report is issued which provides Oncologists with the linkage between the identified genetic mutations and the targeted drugs approved by the major world organizations as well as those undergoing clinical trials and additionally the immunological drugs that have recently entered clinical practice.
There is now a major change in direction regarding the method used for treatment selection in cancer. This modern approach, rather than recommending treatments based solely on the fact that the individual has a specific type of cancer, such as lung, breast, colorectal, etc., instead bases therapy selection by examining the disease at a molecular level. The best way to treat cancer with modern anti-cancer drugs is therefore “agnostic of cancer type”, meaning regardless of the type of cancer a patient may have developed. This is an approach that has been approved by the US Food and Drug Administration (FDA) and that has been adopted by many other countries such as Australia.
These “tumour-agnostic” therapies are beginning to show promising results in the clinical setting, helping patients with a wide variety of different tumours types that have previously been difficult to treat using conventional drugs, especially those patients in second line after the failure of first line treatment. In the tumour center of the Tirelli Medical Group (www.tirellimedical.it) based in Pordenone we have already treated a hundred patients with this therapeutic strategy based on the recommendations of the American Food and Drug Administration (FDA) with often surprisingly favourable results.
Notably this is in keeping with a study recently published in the journal “Oncotarget” by a group of Stanford University in California showing that the use of therapy based on precision oncology (e.g. Oncofocus Test) improves the survival of refractory cancer patients while decreasing the costs of treatment.
Mutations that play a fundamental role in the development of neoplasms have been called “driver” mutations since they are able to confer a growth advantage in the affected cells. Approximately 350 driver genes involved in cancer development have been identified in human tumours. Investigations by massive sequencing have shown that tumours exhibit numerous mutations, most of which are not drivers but “passengers”, i.e. not involved in tumour development but randomly occurring and selected by rapid neoplastic growth.
Knowing the genetic drivers, that is those genetic alterations that are the basis of tumour cell multiplication, means that it is possible to develop precision treatments that specifically and in a completely new way address the choice of biological and immunological drugs.
At the moment, oncologists have limited information in trying to find the right anti-cancer drug for their patient. There are in fact more than 300 anti-cancer drugs and hundreds of different types of cancer, each of these also possesses different genetic mutations that respond differently to therapies, it follows that, even for a good oncologist the chances of finding an effective drug mix can be low.
The use of genetic testing of the tumour biopsy sample is able to help the oncologist in making the right choice by increasing the probability of prescribing an effective drug. Immunological therapy is also identified through this type of testing. Prof. Riccardo Dolcetti, who is a professor of oncological medicine at the University of Queensland in Australia and who has been at the Cancer Institute of Aviano for a long time, tells me that there genetic testing on the tumour tissue is done following diagnosis in the major tumour types (e.g. lung, breast, colorectal, prostate, etc.) but that they also carry out genetic testing on the tumour biopsy taken following relapse if feasible. At the Tirelli Medical Group of Pordenone we carry out genetic testing only in cases of tumoural relapse, that is in patients in whom the first line therapy has failed, even though testing could take place at diagnosis to identify the best treatment available.
Even though the clinical implementation of genetic testing is still not such as to be used in routine clinical practice, it may be in the near future according to what was recently reported in the “New England Journal of Medicine”. The first so-called tumour histology-independent treatment, that is “agnostic of cancer type” was recently recommended by the European for approval in relation to the drug called Larotrectinib. This is a drug that targets a specific genetic mutation called NTRK i.e. the gene coding for the neurotropic tyrosine kinase receptor. Larotrectinib is indicated for the treatment of all pediatric and adult solid tumours that have the NTRK mutation regardless of their tumour type, i.e. whether it is breast, lung, colon, melanoma, etc.
This drug was approved in November 2018 in the United States and is considered an example of a targeted drug that radically changes the approach to cancer treatment. The data that have been recently published in the “New England Journal of Medicine” show an overall response of 76% which is quite unusual for patients heavily pre-treated with conventional therapies who have subsequently been administered Larotrectinib. This genetic alteration can be found in lung, colon, breast, thyroid and melanoma tumours.
Prof. Umberto Tirelli
Director of Tumor Center, Chronic Fatigue, Fibromyalgia and Oxygen-Ozone Therapy,
Tirelli Medical Group Clinic of Pordenone.
Oncologist, National Tumor Institute of Aviano