Mutations to FOXA1 may be key to some aggressive forms of prostate cancer

A newly published study by researchers at the University of Michigan has clarified the potential roles of a transcription factor called “forkhead box A1” (FOXA1) in hormone-driven forms of prostate cancer and some other forms of hormone-driven cancer (e.g., breast cancer).

The new study by Parolia et al., just published in the journal Nature, is also discussed in some detail in what appears to be a media release from the University of Michigan on the ScienceDaily web site.

According to the available information, mutations to the FOXA1 transcription factor could be identified in about 35 percent of a cohort of > 1,500 prostate cancer patients. Neither the abstract of the paper nor the media release seem to indicate the status of these 1,500+ patients. In other words, we don’t currently know if they all had high-risk disease or metastatic disease or what (although this is probably available in the full text of the paper).

Until now there has been a lack of clarity about the role of the FOXA1 transcription factor in the development and progression of prostate cancer. It now appears that — depending upon the precise nature of the mutation — mutant forms of FOXA1 can affect prostate cancer progression in one or more of three different ways:

  • Class-1 activating mutations originate in early-stage prostate cancer, and have been described by the research team as “fast” FOXA1 mutations.
  • Class-2 activating mutations are acquired in metastatic prostate cancers, and have been given the name “furious” FOXA1 mutations.
  • Class-3 genomic rearrangements (“loud” FOXA1 mutations) are enriched in metastatic prostate cancers, and consist of duplications and translocations within the FOXA1 locus

According to Parolia et al., their study

reaffirms the central role of FOXA1 in mediating oncogenesis driven by the androgen receptor, and provides mechanistic insights into how the classes of FOXA1 alteration promote the initiation and/or metastatic progression of prostate cancer. These results have direct implications for understanding the pathobiology of other hormone-receptor-driven cancers and rationalize the co-targeting of FOXA1 activity in therapeutic strategies.

it appears that the Class 1 (“fast”) and Class 2 (“furious”) FOXA1 mutations are mutually exclusive but that Class 3 (“loud”) FOXA1 rearrangements can exist by themselves or mingle with either of the other two.

It seems likely that these findings will lead to studies to see whether specific types of androgen suppression have greater or lesser effects on the progression of prostate cancer in patients with these particular types of mutation, or whether we are going to need a whole new type of treatment to address these particular forms of prostate cancer.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: