2018

Interview of Prof Marc Ansari on personalised medicine and individualised therapies to cure cancer.

The genetic route to chemotherapy

Sometimes the best high tech solutions are the ones that make old technology better.

Take cancer treatment.

At Geneva University Children’s Hospital, Professor Marc Ansari is using cutting edge gene sequencing tools to create individual genetic profiles for cancer patients. His aimis to make sure that each patient has an individualised cocktail of traditional drugs to ensure maximum effectiveness.

Fundamentally, most established cancer-fighting are very effective. The problem is how – and in which dose – to administer them.

And getting this right matters.

Ballpark figures suggest that between a third and a half of people in developed countries will suffer cancer at some point in their lives, while globally, cancers account for more than 16 per cent of deaths. 

Chemotherapy, for example, often comes at an unpleasant cost to the patient: fatigue, hair loss, nausea and infections are routine complications. Minimising the side-effects while maximising the effectiveness of cancer-fighting drugs necessitates getting the dosages just right.

This is where Ansari’s genetic-inspiredtechniques can help.

Therapies need to be made bespoke because different people react differently to the treatmentson offer. Some patients are highly susceptible to the drug regimen’s toxic effects.  Others have ahigher tolerance or process the chemicals rapidly, making normal doses less effective.

“There is too much toxicity in some people, while other people show resistance,” Anasari says.

Meanwhile, how the cancerous cells themselves react to the treatment will also vary.

So, to design the perfect treatment regimen, Ansari’s team analyses the genetics of both the healthy and diseased cells of patients.

“We have to identify which patient has which gene,” he says.

All this hinges on the buildingof database that catalogueshow individuals and cancerous cells with different genetic make-ups have responded to treatments in the past.

To that end Ansari’s organisation, CANSEARCH research laboratory, which runs research projects based at the Geneva University Hospital, has opened studies in more than 20 countries to collect as much DNA evidence as possible. They gather together DNA from across populations – people of different races often have differing responses to a given medication – and from homogenous populations with the same disease – to check how much of a genetic factor affects responsiveness to the given drugs.

“It’s quite simple to identify which patient has which gene and therefore which gene will code for which enzyme and then to see the exact dose we will have to give to the patient,” he says. “What is difficult to see is what’s going to be the cocktail to use, the type of chemotherapy drug. The precision is not only about one drug, but maybe about different drugs that we put together in order to kill that [cancer] cell.”

Developing a comprehensive database is critical to getting the best course of treatment quickly – and speed is particularly of the essence when it comes to treating children.

“Kids are constantly growing so their cells are multiplying very quickly meaning that the cancer development is very, very fast. When kids arrive at the emergency unit we have to very quickly start chemotherapy in order to control the disease,” according to Ansari.

For pharmaceutical companies, the major obstacle to  individualising medicine with existing drugs is cost. Such treatments in childrens don’tgenerate much in the way of additional revenues. Which is why this sort of research is dependent on charities and public bodies, Ansari says.

There is, of course, also a role for entirely new approaches. For instance, Ansari’s team also uses a treatment that alters the genes in one type of a patient’s immune cells so that they will target the cancerous cells.

“It’s called the CAR-T cell, the chimeric antigen receptor T cell. The genetics of your immune system is modified, injecting a virus into some of your cells. The new cells will express a receptor that will target the markers that are at the surface of a cancer cell, in order your immune system will kill the cancer cell,” he says.

The cancer cells often have specific molecular markers on their surface that the modified immune cells then attack.

Unfortunately, this isn’t a magic bullet just yet. As with conventional drugs, modified immune-system cell treatments that target cancers can also have nasty side-effects – in this case they can end up attacking healthy tissue that has the same molecular flags as the cancer, triggering toxicities.

But treatment is constantly being developed and refined.

“Technology is improving all the time so we have more tools in order to analyse and to go further and to answer better” the questions posed by cancer, Ansari says. And the tools will come as a portfolio of treatments rather than as single drugs. “The precision medicine we think nowadays is still a one dimensional medicine whereas probably in a few years it will be multidimensional.”

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2015

Marc Ansari, on behalf of children with cancer

Head of pediatric onco-hematology unit at HUG, this doctor believes that we can do better to improve the lives of children with cancer, including by accelerating research and devising tailor-made treatments. This is why he created the CANSEARCH Foundation.

“Tell me, will I still be sick when I get up there?” This is one of the sentences Marc Ansari, a professor of Geneva University Hospitals (HUG) and head of the pediatric onco-hematology unit has recorded in his notebook.  This is one way to remember the children he has treated. Among the words that have touched him are there are those of Anthony, 15 years old, suffering from a terminal bone tumor. “Well Marc, that’s enough, I want to die now.” Or the request of Leila, who died at the age of 4 years and 3 months: “I would like to have long hair like mom.”

Contact with young cancer patients are part of his daily work. Almost forty to fifty children are treated each year at HUG. A stable figure but with a marked improvement in cure rates. “Our unit has eight rooms that are full to bursting, says Marc Ansari. Curing leukemia, brain tumors or lymphoma was unimaginable 50 years ago. Today we can cure more than 80% of children with cancer, and over 90% of certain types of leukemia.”

However, these figures are not satisfactory for this 43-year-old doctor. He created the CANSEARCH Foundation in 2011 to accelerate research in pediatric oncology. “Childhood cancers are rare diseases that do not particularly interest the pharmaceutical industry as they are just 1% of the total of all cancers, adults and children combined,” he notes.

Better targeted therapies
Last November, 850 people responded to an invitation from CANSEARCH to attend an evening at the Arena in Geneva, collecting over 850,000 francs allowing the Foundation to continue its activities. This has already resulted in the creation of a research platform in the area of pediatric oncology and hematology run jointly with the Faculty of Medicine and HUG. It brings together researchers who want to develop more targeted and less toxic therapies. “Some patients need a transplant of stem cells and must first undergo intensive chemotherapy. About 10% of children do not survive the toxicity of chemotherapy. Moreover, the consequences of these treatments can be dramatic, with heart, lung or brain problems,” says the specialist.

In 2013, the oncologist ‘s team began a global study to sequence the genome of all transplanted children with leukemia to study the interactions between genes and drugs. The team of Marc Ansari is looking to understand how children metabolize these very heavy treatments. “Depending on the genetic profile, we anticipate the toxicity caused by drugs and can thus modify the dosage for chemotherapy and improve the survival rate of patients.”

Almost every child admitted at the HUG is put under research protocol. A genetic profile is automatically performed on each of them to receive a stem cell transplant. “The objective is to arrive at an individual therapy, prescribing the right dose adjusted for age, weight and their genetic profile,” says the specialist. In his wallet, Marc Ansari has his own card with his pharmaco-genetic profile. “I have slower rate of activity in the CYP2B6 cytochrome. I know I would metabolize badly an aspirin or chemotherapy such as cyclophosphamide, “says the doctor who himself experienced serious health problems a year ago while climbing a glacier.

Daily contact with his patients
Father of two daughters, aged 10 and 12, and married for 25 years, Marc Ansari says he draws his resources from his family with whom he never mentions his patients. “I spare my wife and my children who give me strength in my work.”

Born in Geneva, Marc Ansari does not like to talk about himself and even less his childhood memories. His mother sold carpets while his father was studying and the couple divorced when he was very young. As for school, he had a bad start. “I repeated my third grade because I could not read,” he adds.

As a teenager, he worked at Summer camps especially for young people with disabilities. Maybe it was this moment that the idea of caring for children began.  However, he decided to become a diving instructor and left Switzerland for a year to live his passion.

He nevertheless returned to Switzerland to resume his studies and initially chose biology. At 23, he reoriented himself towards medicine all the while doing part-time jobs.  Although he received a scholarship, worked at RTS presenting programs for young people, became a diving instructor and worked in marketing for a pharmaceutical company, he decided, after graduation to go to Montreal for three years to specialize in onco-hematology.

Athough a researcher Marc Ansari nevertheless remains a clinician. He supports and maintains daily contact with his young patients. “Dialogue and contact with parents is fundamental. During the announcement of the disease, the child is rarely present because they would tend to feel guilty seeing their parents cry.”

Although children are generally well supported, distracted and occupied in the pediatric onco-hematology unit, the situation is more complicated for families. “Many parents divorce when faced with their child’s cancer,” says the doctor. Leukemia is two to three years of treatment with often long weeks of hospitalization. However, an employee is only entitled to three days of paid leave per year. Thus, one parent often has to stop working resulting in lower revenues. Added to this, are anxiety and loss of sleep.

“As for the siblings of the sick child, they too pay a heavy price. Their entourage tend to forget their needs,” recalls Marc Ansari who emphasizes a multidisciplinary management of childhood cancers.  “We have to have a lot more resources” he said while welcoming the growing number of foundations that are created around these pediatric diseases.

Ghislaine Bloch article for Le Temps (30/11/2015 )

Also on letemps.ch

 

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2013

Interview: “Eight out of ten children survive cancer”

He calls them “children of the shadows” and it is for them, children with cancer, that Marc Ansari works so hard.  Research, clinic, seeking funds: the forty-year-old doctor is active on all fronts. Saturday, a gala evening organized by the Dubois-Ferriere Dinu Lipatti Foundation will raise funds to support one of its research projects.

While childhood cancer is not of huge interest to pharmaceutical groups – cases are rare – and that there is a shortage public funds, researchers must increasingly turn to the private sector. At the end of 2011, this pediatrician trained in Geneva and Montreal, created a research platform in pediatric oncology and hematology, which brings together researchers from various backgrounds. Their goal is to achieve a personalized cancer treatment which is more effective and less toxic to children.

 

TdG: How many children suffering from cancer are treated in Geneva?

Dr. Ansari: Each year in Geneva approximately thirty children are diagnosed with cancer; we have permanently 8-10 children hospitalized; 80% of them recover. In certain leukemia’s, recovery can be over 90%, which represents fantastic progress as the survival rate was less than 60% in the 1970s.  However, children still die every year in Geneva. Sometimes the treatment does not work or there are relapses. Sometimes with certain types of cancer, we immediately know that we cannot do anything.

TdG: What is the purpose of research today?

Dr. Ansari: The goal is to understand what can save children who relapse. In Geneva, we have the great opportunity of participating in international research programs. In Switzerland, 200 new cases of childhood cancer occur each year. This does not have sufficient statistical power to change the research. This is why we work with Europe and the United States. We work together on protocols and analysis of results in order to improve treatments. It is an incredible opportunity for Switzerland to be part of these networks.

TdG: In Geneva, you have created a multidisciplinary research platform.

Dr. Ansari:  Yes. In late 2011, we established a research platform that focuses on cancer genetics. It is currently developing a dozen projects. Doctors, biologists, pharmacogénéticiens, biostatisticians, immuno-infectious disease experts, bioinformatics: we recruited people in India, England, Italy, France. This diversity of training allows us to analyze a given problem each time from various different angles which is extremely important.

TdG: How is this new?

Dr. Ansari: Without private money, this arrangement would have been impossible. With friends, we set up the CANSEARCH foundation, and found money from private donors, mainly from Geneva such as the Wilsdorf Foundation. The accounts are audited by a private trustee. The foundation is independent of the University and HUG but works in partnership with them. A scientific board is composed of leading experts in the field.

 

Interview by Sophie Davaris for La Tribune de Genève (01/05/2013)

Find the interview and the video on tdg.ch