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Researcher at Childrens Hospital LA discovers way to overcome radiation resistance in leukemia
By Dross at 2010-10-01 22:19
Researcher at Childrens Hospital LA discovers way to overcome radiation resistance in leukemia

LOS ANGELES (September 29, 2010) – A team of researchers lead by Fatih M. Uckun, MD, PhD, of The Saban Research Institute of Childrens Hospital Los Angeles has determined that radiation resistance in leukemiaterm can be overcome by selectively attacking a molecular target known as SYK tyrosine kinase.

B-lineage acute lymphoblastic leukemia (ALL) is the most common cancer occurring in children and adolescents. Despite having received intensive chemotherapyterm, some patients have recurring disease, known as relapse. For these individuals, the prospect of long-term survival is poor.

The standard approach to treating relapsed patients has been additional chemotherapy to achieve a second remission followed by very intensive treatment that could include "supralethal" chemotherapy, total-body irradiation (TBI), and hematopoietic stem cell transplantation. However, radiation resistance of leukemia cells hampers the success of these rigorous therapeutic approaches and results in poor survival.

"We knew that we could kill radiation-resistant leukemia cells if we only knew what made them so resistant. So we set out to determine the mechanism," said Dr. Uckun, who is also professor of Research Pediatrics at the Keck School of Medicine at the University of Southern California. "Once we determined the mechanism, the next step was obvious -- to rationally design a drug that would take out that specific target."

Uckun's research team has now provided the first proof-of-principle that radiation resistance of an aggressive leukemia can indeed be overcome using this rationally-designed specific drug directed against the resistance machinery of leukemia cells.

"Radiation therapy was much more effective against leukemia in mice when it was combined with this new drug candidate that we named C-61," said Dr. Uckun.

 



1 comment | 2494 reads

by gdpawel on Mon, 2010-10-04 04:13
Another area of interest that has been insufficiently explored is the possibility of using cell culture assays to predict a patient's response to radiation therapy.

A Chicago area oncologist, Robert Schrek, at one time applied the assay to the field of radiation therapy. He found that people vary greatly in the susceptibility of their cells to radiation.

One example was that some patients' leukemia cells could be destroyed with a mere two roentgens of radiation, while a few patients had cells that could withstand 1,000 roentgens.

Hinkley and Bosanquet of the Bath Cancer Research Unit reported the results of 61 CLL specimens from 40 patients showed profound inter-patient differences in the sensitivity of cells to radiation. Five patient specimens, which were radio-resistant in vitro, were from patients who were also resistant clinically to irradiation. Another patient who responded very well clinically was found to be extremely sensitive in a cell culture assay.

(Hinkley HJ, Bosanquet AG. The in vitro radiosensitivity of lymphocytes from chronic lymphocytic leukaemia using the differential staining cytotoxicity (DISC) assay. II-results on 40 patients. Int J Radiat Biol. 1992;61:111-121)

Comby, of the University of Caen also observed this relationship in B-cell CLL and predicted the utility of cell culture assays as a valuable clue to the selection of irradiation regimens for B-CLL patients and assessing the impact of radiation on tumor cell death. Investigation of correlations between in vitro radiation-induced apoptosis and the in vivo response to radiation therapy.

(Comby E, Andre I, Troussard X, et al. In vitro evaluation of B-CLL cells apoptotic responses to irradiation. Leuk Lymphoma. 1999;34:159-166)

I understand there are no cell culture assay labs in the world that are currently offering their tests before patients undergoing radiation treatment. It seems likely that adopting research into the use of cell culture assays for pre-screening radiation therapy could be very beneficial.

Differential Staining Cytotoxicity Assay (DiSC)

[url]http://www.ncbi.nlm.nih.gov/pubmed/21516414

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