Une formule mathématique pour guérir du CML.

In people with chronic myeloid leukemia (CML), the drug Imatinib has been shown to drive cancer into remission, but the disease often returns when treatment is stopped. New research by UC Irvine scientists indicates that Imatinib could cure CML under certain circumstances if it is taken over a long enough period of time.

Parmi les gens avec le cancer de la leucémie chronique (CML), l'imatinib a amené des rémissions mais la maladie revient souvent quand le traitement est arrêté. Une nouvelle recherche indique que l'imatinib pourrait guérir le CML sous certaines circonstances si c'est pris pendant une longe période de temps.

Mathematician Natalia Komarova and biologist Dominik Wodarz also developed a tool that eventually could help doctors determine which combination of drugs would be most beneficial to a CML patient, and they determined why, in some cases, Imatinib does not block cancer growth.

La mathématicienne Natalia Komarova et le biologist Dominique Wodarz a développé un outil qui éventuellement pourrait aider les docteurs à déterminer laquelle des combinaison de médicaments serait la plus bénifique pour un patient atteint de CML et détermine pourquoi, dans certains cas, l'imatinib (gleevec) n'arrêtra pas la croissance du cancer.

The drug Imatinib is a promising cancer treatment because it has few side effects, and it specifically targets cancer cells. In their study, the UCI scientists focused on Imatinib and the behavior of cancerous stem cells. Just as normal stem cells maintain organs and a functioning body, cancer stem cells are thought to maintain cancer growth and are tough to kill with treatment.

Many scientists believe that Imatinib can kill regular cancer cells but not stem cells. When treatment ends, the remaining stem cells can produce more cancer cells, thus exacerbating the disease. According to this view, there is no hope to cure CML.

The UCI scientists, however, believe Imatinib can kill cancerous stem cells but not when the stem cells temporarily stop dividing, a state known as quiescence. All cancerous stem cells have the ability to enter the quiescent state. Evidence indicates that when such sleeping stem cells wake up, Imatinib can kill them.

In their paper, the scientists present a mathematical formula that can calculate how long it would take to kill all of the stem cells and cure the cancer. This length of time -- which could be different for each patient -- is based on how often the cancerous stem cells fall asleep and how quickly they wake up. Once the scientists can test their theory with patients, they will be able to determine how long the cure might take.

Dans leur article, les scientifiques présentent une formule mathématique qui peut calculer pendant combien de temps il faut prendre le médicament pour tuer toutes les cellules souches et guérir le cancer.

"There is evidence that a complete cure is possible. Several patients have been reported to have no symptoms after two months without therapy, which is thought to suggest a complete cure," Komarova said. "This evidence supports our theory. Basically, one has to be on therapy long enough for all of the stem cells to wake up and be killed by the drug."

In addition to sleeping stem cells, another barrier to eradication by Imatinib is that cancer cells can mutate to become unresponsive to certain drugs. Conventional thought is that if sleeping stem cells prolong a cure, other cancer cells will have ample time to mutate and become drug resistant.

The UCI scientists, however, have proved this theory wrong. Their calculations show that mutant cells develop early on, in many cases before the patients know they are sick, and do not develop during the treatment process. Using mathematics, they developed a way to calculate the probability that certain mutations exist in a patient. Based on this, one can determine what course of treatment should be used to overcome the resistance.

"The model requires the number of cancer cells that exist, how fast the cells divide and die, and how fast they go to sleep and wake up," Wodarz said. "Once you have those numbers, you can determine how many drugs to use in combination to make sure drug resistant mutants do not become problems."

Inscrit le : 17 Oct 2006 Messages : 167 Localisation : Québec, Qc

Inscrit le : 17 Oct 2006 Messages : 167 Localisation : Québec, Qc

Inscrit le : 17 Oct 2006 Messages : 167 Localisation : Québec, Qc

Parfois il y a des gens qui n'ont pas de connaissances sur le cancer mais qui arrivent à faire plus que beaucoup de gens. Par exemple, un certain monsieur Fesik qui travaillait avec un outil pour voir les cellules en 3 dimensions et avait un talent pour trouver et faire la forme complémentaire à certaines cellules qui pouvaient ainsi bloquer des récepteurs et arrêter le cancer.

l'histoire de monsieur Fesik

Inscrit le : 17 Oct 2006 Messages : 167 Localisation : Québec, Qc

C'est sûr que ce n'est pas un deux de pique au départ mais son histoire m'avait frappé et je trouve qu'il y a quelques enseignements dans cette histoire: - Quelqu'un qui est complètement en dehors d'un gros problème peut mieux voir la solution quelque fois que des gens qui y travaillent depuis longtemps car celui-ci a un esprit totalement neuf devant ce problème. -Le caractère d'une personne est important, quelqu'un d'ambitieux qui y croit fera mieux que quelqu'un qui a est en fin de carrière dont la seule ambition est l'argent et qui n'y croit plus tellement.

Le médicament de la compagnie Abbot m'a l'air très bon et propre à révolutionner les médicaments pour la leucémie. Évidemment pour en être sûr il faudrait que j'ai autant de connaissances que ces gens-là mais c'est le feeling que j'ai à lire sur l'ABT-737.

June 23, 2008 — When kids complain that math homework won't help them in real life, a new answer might be that math could help cure cancer. In a recent study that combined math and medicine, researchers have shown that patients with chronic myelogenous leukemia (CML) may be cured of the disease with an optimally timed cancer vaccine, where the timing is determined based on their own immune response.

Quand les enfants se plaignent que les devoirs de mathémathiques ne les aideront pas dans la vraie vie, une nouvelle réponse pourrait être que les mathémathiques aident à guérir le cancer.Dans une récente étude qui combinait les maths et la médecine, les chercheurs ont démontré que les patients avec le CML pourrait être guéri avec un vaccin donné dans un temps précis, temps en accord avec leur propre système immunitaire.

University of Maryland associate professor of mathematics Doron Levy, Stanford Medical School physician and associate professor of medicine (hematology) Peter P. Lee, and Dr. Peter S. Kim, École Supérieure d'Électricité (Gif-sur-Yvette, France) describe their success in creating a mathematical model which predicts that anti-leukemia immune response in CML patients using the drug imatinib can be stimulated in a way that might provide a cure for the disease.

Des scientifiques ont décrit leur succès à créer un modèle mathématique qui prédit que la réponse du système immunitaire contre la leucémie CML lors de l'utilisation de l'imatinib peut être stimulée d'une mani;re qui pourrait aboutir à la guérison de la maladie.

"By combining novel biological data and mathematical modeling, we found rules for designing adaptive treatments for each specific patient," said Levy, of the University of Maryland Center for Scientific Computation and Mathematical Modeling. "Give me a thousand patients and, with this mathematical model, I can give you a thousand different customized treatment plans."

Math and Leukemia

While the marriage of math and biology is only beginning to catch on in science, there have been other attempts to use equations to understand how leukemia develops and evolves over time. Levy, Lee, and Kim's study differed in that it took into account the patient's natural immune response in conjunction with the effects of imatinib, a drug that has been successful in putting CML patients into remission.

They wanted to see if they could develop a mathematical model, or set of rules, that would increase chances for long-term remission in individual patients. Over four years, Lee's laboratory collected data from CML patients, measuring the strength of each patient's immune response, in the form of the numbers and the activity of the anti-leukemia T cells, at different times during imatinib therapy.

"Our results suggest that it is not only the drug that sends the leukemia into remission, it's also the natural immune response," Levy said. "After starting imatinib, the anti-leukemia immune response gradually increases. However, it begins to weaken after it reaches a peak. This typically happens well into the treatment.

"Leukemia cells are still present, but in relatively low numbers that causes the immune response to wind down. Unfortunately, this is an ideal time for the cancer cells to develop drug resistance and render the therapy ineffective."

Best Time for Immune Response

Incorporating Lee's clinical data on immune response, Levy's model suggests that the immune response of the patients should be boosted at the time when their immune response starts weakening.

Le modèle suggère que la réponse immunitaire des patients pourrait être booster quand cette réponse immunitaire commence à faiblir.

The authors suggest that such a stimulation can be provided in the form of "cancer vaccines," in which pre-therapy blood taken from patients is irradiated to kill active cancer cells, then introduced back to the patient. A strong stimulation of the immune system was shown to be active in vitro in Lee's lab experiments.

"The mathematical approach showed that it is imperative to connect the timing of the cancer vaccine with the individual profile of the immune response of each patient," Levy said. "The mathematical simulations suggest that a vaccine administered within the initial months of the treatment will have no effect on the progression of the disease. On the other hand, a well-timed vaccine can potentially cure the disease."

Individual Therapy Plan

But the dynamics of each patient's immune response differ. That's where the math comes in, says Levy. "We can find rules for application to a specific patient. We can measure each patient's parameters to find when the dosage will be most effective. Mathematics provides the tools that are necessary to tailor the treatment to the patient."

"While some parameters can be measured in the lab," said Levy. "The mathematical model helps us understand the mechanisms that control the disease and show how to use this knowledge to our advantage."

Levy and Lee are currently conducting further extensive study to expand on the results of this research, to prepare for possible experiments on animal models and conduct clinical trials.

«Avec ce modèle mathématique, donnez-moi 100 patients différents et je répondrai par 100 plans de traitement personnalisés», promet Doron Levy, de la Stanford Medical School. Le modèle mathématique de Levy suggère d’administrer un vaccin contre la leucémie au moment précis où la réponse immunitaire du patient s’affaisse.

Lorsqu’on administre le médicament, la réaction immunitaire antileucémie augmente graduellement. Elle atteint son apogée, et élimine en grande partie les cellules cancéreuses. Alors devenues rares, elles ne stimulent plus les défenses immunitaires, qui s’affaiblissent.

Malheureusement, c’est à ce moment que les cellules cancéreuses développent une résistance qui rend la thérapie inefficace. En fouettant le système immunitaire avec un second traitement — un vaccin — à ce moment précis, le traitement pourrait faire la différence entre la rémission et la mort.