Medindia

X

New Genetic Studies Carried Out in Cancer Therapy

by Medindia Content Team on  June 18, 2007 at 3:00 PM Research News   - G J E 4
New Genetic Studies Carried Out in Cancer Therapy
The researchers identified individual genes that are associated with resistance to chemotherapeutic drugs and sets the stage for future studies that may significantly enhance the ability to predict whether or not a particular tumor will respond to treatment,using a functional genomic screen.
Advertisement

Resistance to chemotherapeutic drugs is the primary cause of treatment failure in patients with metastatic cancer. Dr. Julian Downward from the Cancer Research UK London Research Institute and colleagues used RNA interference to directly examine the contribution of over 800 candidate proteins to the sensitivity or resistance of cancer cells to several drugs that are commonly used to treat cancer.

Advertisement
Using this technique, the researchers found that resistance to the chemotherapeutic agent paclitaxel, a member of the taxane family, as expected, involves genes that impair drug-induced mitotic arrest following knockdown. Silencing of these genes in many cases also induces polyploidy and multinucleation in the absence of drug treatment.

The researchers conclude that specific disruption of the mitotic checkpoint promotes paclitaxel resistance and that chromosomal numerical heterogeneity may be a useful predictor of paclitaxel resistance in some cancers.

Ceramide metabolism was identified as a critical regulator of sensitivity to a wide range of chemotherapeutic drugs. Although ceramide has been associated with apoptosis for some time, the mechanisms have not been well understood.

In this study, decreased expression of a ceramide transport protein, COL4A3BP, sensitized cancer cells to multiple cytotoxic agents. Further, expression of COL4A3BP was increased in drug-resistant tumor cells and in a small cohort of ovarian cancers following paclitaxel treatment.

The researchers suggest that paclitaxel-induced prolonged mitotic arrest may result in ceramide accumulation and initiation of apoptosis, while inhibition of this arrest, characterized by polyploidy, may suppress ceramide generation and promote cell survival.

"These data suggest that the taxane class of drugs may lack efficacy in tumors with high levels of chromosomal instability characterized by chromosomal numerical heterogeneity and provide a rational basis for identification of patients likely to benefit from these drugs," explains Dr. Downward.

Source: Eurekalert
LIN/S
Advertisement

Post your Comments

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
User Avatar
* Your comment can be maximum of 2500 characters
Notify me when reply is posted I agree to the terms and conditions

You May Also Like

Advertisement
View All