Gynecological cancers - Frédéric SELLE, MD


Dr Frederic Selle

Gynecological cancers represent a very important area of research for APREC

The university-based Tenon Hospital, at the center of East Paris university hospital system, contains a center named “expert in gynecological cancerology,” and as such it benefits of a large recruitment of patients. The management of these cancers requires the simultaneous presence of specialized surgical teams, a surgical rehabilitation unit (due to the often extensive surgical interventions required by these cancers) and other medical teams in constant cooperation (radiologists, pathologists, radiotherapists, medical oncologists).  This highly specialized multi-disciplinary structure is both a guarantee that patients will receive the best care, and a unique place in which to pursue research.

The clinical research APREC conducts within this structure, through “clinical trials” of phase I, II, III,  aims to confirm the effectiveness of new molecules that then might obtain an “AMM” (Autorisation de Mise sur le Marché – the equivalent of FDA approval) and thus be of benefit to all.  But before then, for the patients who participate in these trials, it also guarantees early access to therapeutic innovations.

The second area of research conducted by APREC is “transfer research,” which attempts to decipher the cellular and bio-molecular mechanisms of tumors.  In fact, at Tenon Hospital there is a Tumor Repository where samples taken from the tumors of each of the patients being treated for gynecological cancer at Tenon Hospital, are frozen and stored.  These samples are used in research studies of the genome of each tumor, the results of which are correlated with the clinical history of the patient.  The objective is to identify genomic abnormalities specific to each tumor, which then become “therapeutic targets” for the development of new so-called “intelligent” or “targeted ” molecules.

And so APREC is involved in several innovative therapeutic approaches to treating ovarian cancer:

  • The first is to develop through therapeutic trials a significant tool in cancerology, that of targeted molecules called “antiangiogenic.” The function of these molecules is to block the vascularization of tumors, which is indispensable to their growth.  A certain number of molecules in clinical development (pazopanib, nintedanib, cediranib, trebananib) have been proven to be effective, and one of them (bevacizumab) has already obtained AMM approval.
  • Another therapeutic approach in which APREC is involved is that of immunotherapies.  In fact, ovarian cancer is a tumor implanted within a host and which thus interacts with the environment and notably the immune system.  Cancer cells are aberrant cells that a priori should be eliminated by the organism; but they escape the immune defenses through various mechanisms.  APREC has invested a great deal in the development of molecules that reinforce the immunity of the organism against the tumor, and important work has been focused on a molecule called lenalidomide.  This work has been the object of recent presentations at the largest cancerology meetings, such as ASCO (American Society of Clinical Oncology).
  • The Tenon Hospital is called a “Centre des femmes à risque génétique” (center for women at genetic risk), and a large number of women who go there present a genetic mutation BRCA1 or BRCA2.  This mutation exposes them to an increased risk for breast cancer, but also for ovarian cancer (ten to fifteen percent of ovarian cancers are related to this genetic predisposition).  The mutation BRCA1 or BRCA2 is responsible for a defect in the  mechanisms of   DNA repair , which is responsible for the cancerization of the cell.  We have found the means to “inverse” the defect in DNA repair and to make it turn around like a boomerang against the cancerized cell.  To do this, we use molecules called PARP inhibitors (Poly-ADP Ribose Phosphate inhibitors).”  They constitute one of the most promising therapeutic class of drugs, and have already proven spectacularly positive results in the first studies in which APREC has been involved.

These few examples illustrate APREC’s essential role in cancer research and in the battle being waged against cancer.

My name is Frédéric Selle.  I am a medical oncologist in the oncology unit at Tenon Hospital in Paris, and a member of the Scientific Board of APREC, responsible at the national and international levels for the development of clinical research in gynecological cancers.

In the past ten years we have witnessed a great deal of progress in the realm of gynecological cancers, notably in ovarian cancer.  This progress is related in part to better patient care, notably with regard to usual difficulty of surgery, the quality of which can only be assured in highly-specialized centers of care. Today more and more patients have access to these centers, where they find the right  treatment they require.  These centers of expertise are also places where, through access to clinical trials, patients can have access to therapeutic innovations in chemotherapy and other new drugs. The progress is related in another part to our knowledge of the cellular and molecular biology of these tumors, which is improving astronomically, enabling us to better understand their behavior and for instance what causes them to resist chemotherapy.  We are now able to better understand the intimate mechanisms of cancerogenesis and to identify, in each tumor of each patient, specific cellular and molecular abnormalities against which we can act thanks to so-called “intelligent”or “targeted” molecules.  Not only are we in a position to identify the targets on tumor cells, to use specific molecules on those targets, but we also know from scintigraphy, genetic, or microscopic testing how to select patients who would be candidates for such targeted treatments .

An example to illustrate this modern approach: today we can identify patients who carry the BRAC1 – BRAC2 mutation.  It is widely known that these mutations expose carriers to a higher risk of breast cancer, but this is also true of ovarian cancer.  This mutation is responsible for a defect in the mechanisms of DNA repair, which is responsible for the appearance of the cancer.  Our therapeutic ruse has been to use this repair defect, and to carry it to turn around against the cancer cells themselves, by using molecules called PARP inhibitors, whose effectiveness is extremely promising.  This example shows that we are capable of attacking cancer cells at their innermost core, and the work carried out by highly specialized teams such as those at APREC today make us extremely hopeful for the future of cancer treatments.