Does RAF gene rearrangement cause an aggressive but treatable subtype of prostate cancer?
Posted Jun 09 2010 12:00am
According to a media release from the Prostate Cancer Foundation yesterday, research at the University of Michigan Comprehensive Cancer Center suggests that the RAF oncogene that drives fatal forms of melanoma (an aggressive type of skin cancer) may also drive aggressive forms of prostate cancer.
It has long been understood that there are certain types of prostate cancer that are clinically much more aggressive than others. One such example is small cell carcinoma of the prostate, which is commonly found in younger men and has an extremely aggressive clinical profile. It now appears that there may be a subtype of adenocarcinoma of the prostate that is associated with genetic rearrangements (“gene transfusions”) that affect a biochemical pathway called RAF, which is known to play a role in cancer cell metastasis and death.
There had been no evidence that the RAF pathway or the RAF kinase enzymes were specifically involved in the biology of human prostate cancer until this recent finding. The good news is that four “anti-RAF” drugs have already been developed and have entered clinical trials. The work published by Palanisamy et al. in Nature Medicine this week suggests that these RAF inhibitors could be an effective treatment for prostate cancer patients with this gene fusion marker.
The RAF gene fusions are rare apparently occurring in only about 2 percent of prostate cancers. However, if the patients with RAF gene fusions are at significantly higher risk for aggressive prostate cancer leading to prostate cancer-specific mortality, then the ability to prevent or delay disease progression in these patients might still have a significant impact on overall prostate cancer mortality. That 2 percent of the men who are diagnosed with prostate cancer each year translates into about 10 to 15 percent of the number of men who die from prostate cancer each year.
It is worth noting that these newly discovered RAF gene fusions do not occur in cancers with the previously discovered and widespread gene fusions (i.e., the ETS-based gene fusions that are seen in about half of all prostate cancer cases), and the new RAF-based fusions do appear to be linked to more clinically aggressive cancers.
According to Dr. Arul Chinnaiyan, the senior author of this new piece of research, “Rather than treating cancer as just an entity classified under the microscope as a ‘prostate tumor’ … it needs to be thought of as a ‘RAF mutant tumor.’ We need to think about what the driving molecular basis for each tumor is and what oncologists can then do about that for the patients.” This type of thinking has already become more common in how we think about many of the “blood” cancers like leukemias and lymphomas, as well as in breast cancer, where you commonly hear people talk about HER2 positive and HER2 negative types of tumor, which then respond to differing types of drug.
Over the next few years The “New” Prostate Cancer InfoLink believes we will see an increasing ability to identify the underlying biology of several of the more aggressive subtypes of prostate cancer. This may allow us to treat these subtypes with much greater specificity leading to a significant reduction in the risk of prostate cancer-specific mortality. If, for example, we were able to better treat (say) six aggressive subtypes of prostate cancer which are the ones associated with the highest levels of risk for prostate cancer-specific mortality, and those subtypes were associated with 15 percent of all prostate cancer diagnoses, that would translate into the potential to eliminate nearly all prostate cancer-specific deaths!