Therapy exploits 'addiction' of leukemia cells

April 16, 2012

A new study describes a therapeutic approach to halting cancer progression by exploiting a previously unrecognized "addiction" of leukemia cells to specific signaling molecules. The research, published by Cell Press online on April 16th in the journal Cancer Cell, identifies non-classical oncogenes critical for tumor development and survival, and describes a potentially less toxic strategy that selectively targets these molecules.

Many cancers are associated with the loss of function of the PTEN , including T-cell (T-ALL). Loss of PTEN leads to unbridled activation of the PI3K/Akt signaling pathway that drives and survival. "We know that there are multiple types of PI3K molecules, designated PI3Kα, β, γ, or δ, the unrestricted activities of which could contribute to these processes," explains senior study author, Dr. Thomas Diacovo, from Columbia University Medical Center. "However, what role, if any, distinct PI3K subtypes play in the pathogenesis of T-ALL was unknown."

Using a mouse model of T-ALL, Dr. Diacovo and colleagues found that in the absence of PTEN, the unrestricted activity of either PI3Kγ or PI3Kδ was sufficient to support and that deletion of both subtypes was required to impair the development of T-ALL. "We found that these two molecules act as a kind of bottleneck in the progression of T-ALL and that the cancer cells can become addicted to these two specific signaling molecules," says Dr. Diacovo. The researchers went on to show that dual inhibition of both PI3K subtypes was necessary to prolong survival of mice with T-ALL and to promote the death of human tumor cells.

"Our work represents a significant advancement in the understanding of the dynamic interplay that exists between PTEN and specific PI3K subtypes in regulating both normal and abnormal T cell development, as well as in sustaining tumor proliferation and survival," concludes Dr. Diacovo. "By pinpointing these therapeutic targets, it may be possible to limit the toxicity that is associated with current T-ALL therapies and to avoid the potential global impact that less selective inhibition of the PI3K/Akt signaling pathway may have on cancer patients."

Explore further: Study identifies potential treatment for lethal childhood leukemia

More information: Subramaniam et al.: "Targeting non-classical oncogenes for therapy in T-ALL." Cancer Cell April 17, 2012/ DOI:10.1016/j.ccr.2012.02.029

Related Stories

Study identifies potential treatment for lethal childhood leukemia

April 16, 2012
Columbia University Medical Center (CUMC) scientists have demonstrated that two related enzymes — phosphoinositide-3 kinase (PI3K) gamma and delta — play a key role in the development of T-cell acute lymphoblastic ...

New breast cancer model of mutant PI3K recapitulates features of human breast cancer

July 12, 2011
Scientists from the Friedrich Miescher Institute for Biomedical Research have shown that a mutation in the lipid kinase PI3K, which occurs in about 30% of human breast cancers, itself evokes different forms of breast cancer. ...

Recommended for you

Bolstering fat cells offers potential new leukemia treatment

October 16, 2017
Killing cancer cells indirectly by powering up fat cells in the bone marrow could help acute myeloid leukemia patients, according to a new study from McMaster University.

Study reveals complex biology, gender differences, in kidney cancer

October 13, 2017
A new study is believed to be the first to describe the unique role of androgens in kidney cancer, and it suggests that a new approach to treatment, targeting the androgen receptor (AR), is worth further investigation.

Cholesterol byproduct hijacks immune cells, lets breast cancer spread

October 12, 2017
High cholesterol levels have been associated with breast cancer spreading to other sites in the body, but doctors and researchers don't know the cause for the link. A new study by University of Illinois researchers found ...

New drug hope for rare bone cancer patients

October 12, 2017
Patients with a rare bone cancer of the skull and spine - chordoma - could be helped by existing drugs, suggest scientists from the Wellcome Trust Sanger Institute, University College London Cancer Institute and the Royal ...

Scientists pinpoint surprising origin of melanoma

October 12, 2017
Led by Jean-Christophe Marine (VIB-KU Leuven), a team of researchers has tracked down the cellular origin of cutaneous melanoma, the deadliest form of skin cancer. The team was surprised to observe that these very aggressive ...

Team finds a potentially better way to treat liver cancer

October 12, 2017
A Keck School of Medicine of USC research team has identified how cancer stem cells survive. This finding may one day lead to new therapies for liver cancer, one of the few cancers in the United States with an incidence rate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.