April 8, 2006

Researchers Use Targeted Therapies that Distinguish Cancerous Cells from Healthy Cells

(RedOrbit) It is widely known that one drawback of current cancer treatments is that while tumor cells are targeted and killed, some healthy cells may also be killed in the process.

Researchers are looking for ways to more effectively target cancer cells without harming their healthy neighbors, a process know as targeted therapy.

Three candidates for targeted therapies are highlighted below.


Researchers from the National Cancer Institute (NCI) in Bethesda, Md., have found they may be able to successfully treat brain tumor cells with a drug called bortezomib or (Velcade®.) This targeted therapy inhibits the activity of a cell protein called nuclear factor-Kappa B (NF-kB.)

NF-kB appears to be related to tumor progression and treatment with bortezomib suppressed the activation in NF-kB thus stopping growth of cancer cells.

NF-kB is a good candidate for targeted therapy because high levels of activated NF-kB are found in transplanted glioma cells and glioma tumor samples, but not in normal brain tissue cells.

"Targeting the NF-kB pathway either alone or in combination with other chemotherapy agents, is an effective anti-glioma treatment," said Ai-Min Hui, M.D., Ph.D., research fellow at the NCI and the lead investigator of the study.


Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, Tx., have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin®) or may even develop a resistance to it.

Trastuzumab treats women with metastatic breast cancer whose tumors overproduce the ErbB2 gene. ErbB2 overexpression leads to aggressive breast cancer and poorer patient survival. Still, many patients develop resistance to trastuzumab over time.

Researchers found that loss of the tumor suppressor gene PTEN can lead to resistance of trastuzumab. Normally, the PTEN enzyme causes cells to stop dividing however, loss of PTEN causes excessive cell growth and contributes to trastuzumab resistance.

Researchers showed that a certain phosphoinositide 3-kinase (PI3K) pathway inhibitor, when used in combination with trastuzumab, was able to reverse PTEN-reduction-mediated trastuzumab resistance and successfully inhibit cell growth.

"PTEN seems to be a very sensitive and specific predictor to trastuzumab-based therapy and data suggest that activation of PTEN is a novel mechanism underlying the anti-tumor activity of trastuzumab.


Researchers from OSI Pharmaceuticals have identified an IGF-1R inhibitor (referred to as Compound 1) that may stop the growth of colon cancer.

Insulin-like growth factor 1 receptor (IGF-1R) is an important treatment target for many human cancers such as colorectal, non-small cell lung and ovarian because these tumors drive their own growth and survival through activation of IGF-1R, thus making it a good candidate for targeted therapies.

IGF-1R has been shown to play roles in tumor cell growth and the inhibition of cell death. By blocking IGF-1R signaling with Compound 1 researchers may have found a way to selectively treat certain cancers.

By Karen Ventii of RedOrbit from Wire reports

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