The substance, in combination with the drug Glivec, was able to "turn off" the cells responsible for disease
Researchers have managed to overcome resistance to treatment of a form of leukemia, demonstrating the complete eradication of cancer in studies with animal cells. The study shows that an experimental drug, RI-BPI in combination with the drug Glivec, off the stem cells responsible for about one third of leukemia acute lymphoblastic (ALL), a cancer of white blood cells that affects both children and adults.
ALL have known Philadelphia chromosome, which is also found in chronic myeloid leukemia (CML). But although Gleevec has improved very survival in CML, it had a less significant effect in ALL, and most patients still die within a relatively short time.
"This desperate prognosis can radically change the face of these results. I am surprised and extremely happy to see that the RI-BPI has such strong activity on leukemia. This opens the possibility that the agent has the same beneficial effects in other tumor types, " says researcher Ari Melnick.
RI-BPI have shown potent effects on non-Hodgkin lymphoma (HNL) without toxicity to normal cells. The drug attacks the transcription factor BCL6, a master regulator of hundreds of genes provides strong growth signals to the cell NHL.
Melnick said the new study also showed that BCL6 acts on ALL driven by the Philadelphia chromosome (Ph ALL) and a combination of RI-BPI and virtually paralyze Glivec cancer. After a long search for the source of resistance to Glivec in this form of ALL, the team observed that BCL6 appears to be the key mediator in this process. "This gives us an opportunity to attack resistance to Gleevec, thus have the potential to substantially improve outcomes for patients with this disease, "he explains.
The team found that the production of BCL6 is initiated after the administration of Glivec in Ph ALL. Next , began the research in collaboration with Melnick, who provided the RI-BPI and conducted experiments on how the BCL6 regulates genes in cells with leukemia. The researchers also conducted tests with plow animals and found that the BCL6 reaches the stem cells that give rise to ALL. "These stem cells continuously repopulate diseased cells, making copies of themselves. We believe that the RI-BPI against the BCL6 gene regulatory program that these stem cells need to survive. The BCL6 off the brakes that normally limit the growth of cancer, why Gleevec does not work in this cancer, but the RI-BPI triggers these brakes again, "said Melnick.
The study also suggests that the transcription factors such as BCL6 may be less than previously thought impervious to specific treatment. The BCL6 protein is a media and their actions cancer by joining with other proteins. Traditionally, however, the protein-protein interactions have been viewed as difficult to block with drugs small molecules.
Although it has yet to be tested in refractory CML - CML resistant to Gleevec, which occurs in most patients over time - makes sense, according to Melnick, the RI-BPI could restore sensitivity to Gleevec.
"From this and other studies in my lab, I was very impressed with how the tumor cells are dependent on certain proteins for their survival. If we can hit several of these cases fragile and dependent, have the opportunity to eradicate cancer "says the researcher. Based on this study, a clinical trial is being developed for the treatment of children with Ph ALL with a combination of RI-BPI.
Source: http://www.isaude.net
0 comments:
Post a Comment