AACR Annual Meeting 2013
Prevention of squamous cell carcinoma
Dr Kenneth Tsai – MD Anderson Cancer Center, Houston, USA
My lab has been interested in cutaneous squamous cell carcinoma for some time. We actually initially started our research several years ago looking at the development of squamous cell carcinomas and BRAF inhibitor therapy, in particular vemurafenib and Plexxikon 4720, and we actually explored some mechanisms related to off-target effects of these drugs. In more recent years we’ve turned our attention to looking at the progression sequence to cutaneous squamous cell carcinoma from irradiated skin to the precancerous lesion, the actinic keratosis, onto invasive carcinoma. And this is the work that has been recognised by the Landon Foundation in the Cancer Prevention Award this year. We’ve undertaken a comprehensive genomic approach to try to understand the drivers of this transition in the hopes of identifying better ways of predicting progression as well as better ways of interrupting that process.
It’s thought that a minority of AKs, these precancerous actinic keratoses, eventuate in invasive carcinomas but we actually have no way of identifying which ones will progress. In the United States and Australia and Europe, most parts of Europe, these lesions are pretty aggressively treated; in fact, they’re often treated without any histologic assessment or anything like that because there’s that risk of progression to carcinoma. And that’s practical for many people; unfortunately for very high risk individuals, people who are immunosuppressed, for example, or who have had so much UV exposure that large parts of their skin are involved, many of these therapies which are destructive in nature are often difficult to tolerate, they’re very inflammatory, patients don’t like them. So we’re looking for ways to identify which lesions are most likely to progress, so those can be targeted more specifically. And, conversely, identifying individuals that are at low risk or lesions that are at low risk, we can avoid treating things that don’t need to be treated.
We did next generation sequencing, RNA sequencing as well as micro-RNA sequencing, and we’ve just started to identify a handful of micro-RNAs that we’re just now beginning to validate in our studies. We have a few that seem promising, that seem to be able to distinguish which actinic keratoses may be involved but it’s still in the relatively early stages right now.
Are these types of tumours more related to UV damage than melanoma?
I would say that epidemiologically these tumours are overwhelmingly the result of excessive or inappropriate UV exposure. The story with melanoma, I think, is a little bit more complicated, certainly the genomic evidence suggests that there is a large component of UV exposure that’s involved but there are also other drivers, environmental drivers, in melanoma that are a little less well characterised.