Targeted therapies at Institut Curie

What are targeted therapies?

Targeted therapies, which are proposed before or after a surgical intervention, alone or in combination with another anti-cancer treatment, participate in the curative strategy for cancers. Today, one in three anti-cancer medicinal products is a targeted therapy¹ .

Targeted therapies belong to so-called precision or personalized medicine. It is the molecular profile of the tumor, specific to each patient, and not the location of the tumor, which will steer the choice towards a targeted therapy. 

 

The key principles of targeted therapies

Targeted anti-cancer therapies are medicinal products that aim to deactivate the mechanisms responsible for the growth and proliferation of tumor cells by specifically targeting the abnormalities of the tumor. In particular, they target abnormal proteins present in cancer cells, on their surface, or in their environment. These abnormal proteins – called oncogenic – are the consequence of genetic modifications (mutations) in the DNA or RNA of the cells causing the cancer. By targeting these abnormalities on which tumor cells are highly dependent, targeted therapies aim to cause cell destruction. The objective: to slow the progression of the disease, or even cause the tumor to shrink.

Molecular tests are carried out on all patients in order to identify the specific abnormalities of their tumor, and thus to adapt their treatment according to these abnormalities, which are considered targets to be aimed for. The target becomes a way of classifying and therefore treating cancers. Several targeted therapies can be authorized for the treatment of the same type of cancer if different targets have been identified. Conversely, the same targeted therapy can work on cancers located in different organs if they have the same molecular characteristics. 
Targeted therapy is usually a long-term treatment. Since it does not have a lasting effect, it must be continued to maintain an antitumor action. Thus, some targeted therapies are administered until there are no more signs of cancer, while others can be continued for life, or until their effectiveness ceases due to the appearance of resistance. 
 

Modes of action of targeted therapies

Several targeted therapies with different modes of action make it possible to reach the identified tumor targets: 
•    Intracellular inhibitors: these are small molecules that will penetrate cancer cells to target an abnormal protein and block the oncogenic mechanism. This treatment is administered orally, in the form of tablets, and is taken at home.  
•    Monoclonal antibodies: these large molecules act outside the cell, on protein targets present on the surface of cancer cells, or in their environment. This treatment is administered by intravenous or subcutaneous perfusion, in the hospital or at home. 
There are also hybrid medicinal products, chemotherapy-conjugated antibodies (CDA), which make it possible, through targeted therapy, to bring doses of chemotherapy as close as possible to the tumor.  

 

Adverse effects of targeted therapies

Targeted therapies are "selective" drugs that specifically attack cancer cells by targeting their abnormalities, thus sparing healthy cells. However, this does not mean that they are completely devoid of undesirable effects. The latter vary depending on the intended target: fatigue, gastrointestinal disorders, skin rashes, cardiovascular complications, cognitive disorders, etc. 
These undesirable effects can be alleviated through appropriate preventive treatments (such as anti-diarrhea drugs) or practical advice. They are usually reversible and disappear when the treatment is discontinued. 

 

[1] Source INCa

The expertise of Institut Curie in targeted therapies

Molecular tests

Before any targeted therapy is implemented, molecular tests are carried out for each patient in order to characterize their specific tumor and to find the cancer’s "Achilles heel", in other words the target to be attacked. At Institut Curie, these innovative molecular tests are carried out within the hospital platform for molecular genetics of cancers, after biopsy of the tumor (in most cases) or blood sampling. 
When a target is identified in a patient, targeted therapy often proves to be highly effective. High response rates are usually noted, characterized by a reduction in the size of the tumor – especially in lung cancer, the cancer most commonly treated with targeted therapies. 
 

Research priorities at Institut Curie

Even though there are many targets that are already known, Institut Curie actively participates in research and discovery of new targets in order to develop the next generations of targeted therapies. The challenge is to treat cancers that cannot currently benefit from this treatment, or to be able to offer other options to patients who are already undergoing targeted therapies that have become less effective.

Indeed, under the pressure of targeted therapy, the tumor is able to defend itself by expressing other targets. Resistance mechanisms may then appear, and the targeted therapy may gradually become less effective. In this case, adapting the treatment by looking for new tumor targets is necessary. This is one of the objectives of the molecular MDT (multidisciplinaryteam meeting), which was set up in   2014 at Institut Curie. Every year, numerous patient cases are discussed in order to adapt the therapeutic strategy using targeted therapies, or even to direct them towards early clinical trials. 


 

Compliance issue

Since targeted therapy is a long-term treatment, there is a real challenge in terms of therapeutic compliance (degree of patient compliance with the drug prescription) and long-term patient monitoring. In order to meet these needs, in 2024, Institut Curie opened a day hospital for oral therapies within the Department of Medical Oncology, which is accessible to patients undergoing targeted therapy and to all those taking oral anti-cancer treatment. This day hospital is a special service offered by the institute, and it provides multidisciplinary care that takes into consideration the quality of life of patients. In particular, there are nurses who manage and prevent side effects that may appear during treatment.