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

Drug suppresses spread of breast cancer caused by stem-like cells

December 12, 2017
Rare stem-like tumor cells play a critical role in the spread of breast cancer, but a vulnerability in the pathway that powers them offers a strategy to target these cells using existing drugs before metastatic disease occurs, ...

MRI scans predict patients' ability to fight the spread of cancer

December 12, 2017
A simple, non-invasive procedure that can indicate how long patients with cancer that has spread to the brain might survive and whether they are likely to respond to immunotherapy has been developed by researchers in Liverpool.

A new weapon against bone metastasis? Team develops antibody to fight cancer

December 11, 2017
In the ongoing battle between cancer and modern medicine, some therapeutic agents, while effective, can bring undesirable or even dangerous side effects. "Chemo saves lives and improves survival, but it could work much better ...

Insights on how SHARPIN promotes cancer progression

December 11, 2017
Researchers at Sanford Burnham Prebys Medical Discovery (SBP) and the Technion in Israel have found a new role for the SHARPIN protein. In addition to being one of three proteins in the linear ubiquitin chain assembly complex ...

Glioblastoma survival mechanism reveals new therapeutic target

December 11, 2017
A Northwestern Medicine study, published in the journal Cancer Cell, has provided new insights into a mechanism of tumor survival in glioblastoma and demonstrated that inhibiting the process could enhance the effects of radiation ...

Liver cancer: Lipid synthesis promotes tumor formation

December 11, 2017
Lipids comprise an optimal energy source and an important cell component. Researchers from the Biozentrum of the University of Basel and from the University of Geneva have now discovered that the protein mTOR stimulates the ...

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.