22 million new cases occur every year. Such is the predicted magnitude of cancer in 20 years’ time, according to the World Health Organization. To cope with this challenge, researchers are fighting the disease on an increasing number of fronts. The teams at Servier have chosen to concentrate on three of them.
“Fifteen years ago, diagnosis of metastatic melanoma meant a rapid fatal outcome. Today, it is possible, with treatment, to expect a 5-year survival. And the field is changing at an extraordinary rate!” In an interview they granted to the academic journal “Future Oncology,” Patrick Therasse (Head of Clinical Development, Oncology) and Jean-Pierre Abastado (former Director of Oncology R&D) express their optimism. And for good reason: fighting cancer is advancing fast.
An arsenal against cancer
Although the therapies have advanced, it is above all thanks to such a considerable effort that the knowledge accumulated has enabled a better overall understanding of the mechanisms involved in the disease: processes for triggering cancer, interactions between cancer cells and the immune system, the spread of cancer cells in the body, and so on.
Above all, cancer treatment is evolving, from largely non-selective cytotoxic chemotherapy – which destroyed a large number of healthy cells along with the cancer cells – to targeted and personalized therapies.
“Targeted” means that they can recognize the specific components of cancer cells (receptors, proteins, etc.), or act at a specific stage in their development. “Personalized” means that they are tailored to the specific genetic and biological characteristics of the patient’s tumor cells.
The consequence? More effective long-term treatments, less severe and better controlled side-effects, and less time lost to unsuitable treatments.
A winning strategy
In order to allow patients to benefit from these advances, Servier has chosen to deploy the resources to succeed, to choose the right partners, and to target its efforts.
In terms of resources, the figures speak for themselves: the group allocates 35% of its R&D budget to oncology, and anticipates increasing this effort to 50% in the next two years.
In terms of choosing the right partners: this was already well established in late 2016, 19 partnerships were in place, with both academic (CNRS, Institut Curie, Institut Gustave Roussy, Singapore Immunology Network, Walter and Eliza Hall Institute in Australia) and industrial partners (from biotech companies like Cellectis, Macrogenics and more recently Pieris, to the major players in the pharmaceutical sector, like Novartis and Pfizer).
The object of these partnerships? To tap into additional expertise and thereby speed up research and the development of new drugs.
To achieve this, Servier has chosen to target its efforts by opting for three types of strategy: targeted therapies, apoptosis and immuno-oncology. Particularly promising areas, in which Servier already has expertise.
Better targeted treatments
On the targeted therapy front, Servier is focusing a particular effort on one family of enzymes. These are the tyrosine kinases. Why are they of interest to our researchers? Because tyrosine kinases contribute to cancer progression.
Thus one kinase inhibitor, S49076, originating from research at Servier, is now in the clinical studies phase, i.e. being tested in patients with certain types of non-small-cell lung cancers.
Making cancer cells die
On the second front – apoptosis – the object is to make cancer cells die. Apoptosis is actually a natural phenomenon of programmed cell death, in which the body destroys cells that have become useless or abnormal. The ability to avoid apoptosis is one of the key characteristics of cancer cells – and a relatively common mechanism of resistance to treatment.
One particular family of proteins, the BCL-2 family, is currently attracting all the attention. Overexpressed in cancer cells, these proteins prevent the cells from entering apoptosis, and hence from dying. This is referred to as tumor survival. The goal of research carried out by Servier is to target these proteins accurately, in order to trigger the mechanism for programmed cell death in these cancer cells.
Research conducted by our company on one of these proteins has been the subject of a scientific publication in the prestigious journal Nature.
Boosting the immune system
Finally, the third research front is immuno-oncology. The idea? To restore and boost the immune system in order to enable it to recognize and destroy cancer cells. In other words, the drugs administered to patients no longer target only cancer cells but also stimulate the immune system, which itself attacks the tumor. Why choose this strategy rather than another one? Because immuno-oncology is already showing promising results, especially in diseases with a very poor prognosis, such as lung cancer or skin cancer at an advanced stage.
To properly understand what is involved, it is necessary to know that the immune system acts through a whole set of immunological check-points. Malignant tumors protect themselves by tricking the cells of the immune system, which allow them to escape. The researchers have identified new antibodies known as “check-point inhibitors,” that can prevent tumors from escaping the immune system.
Will the battles fought on these three research fronts cause cancers to retreat? The researchers have no doubt that they can improve life expectancy and quality of life for patients, or even obtain long remission. However, they emphasize that a joint approach involving more than one therapeutic option will make it possible to obtain better results. Through the partnerships it has forged and the resources it has mobilized, Servier is thus at the forefront of the fight against cancer, an increasingly targeted and focused battle, and a source of hope for patients.
Average &D investment by Servier over the last 5 years: €800 million
35% of research funds devoted to fighting cancer
3 cancer products on the market in 2017
9 products in clinical development
19 current partnerships
 The tyrosine kinases are a family of enzymes involved in signaling pathways that contribute to the spread of cancer cells.
 A kinase inhibitor can block the action of one or more kinases. S49076 is an inhibitor of MET and AXL kinases.
 “The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models.” 538, 477-482, 2016.