EACR 2016

Towards deciphering the functional genetics and neo-antigenic landscape in melanoma

Prof Yardena Samuels - Weizmann Institute of Science, Rehovot, Israel

I’ll be talking about our work, actually ever since I opened my lab which was ten years ago, aiming to decipher the melanoma genetic landscape, so I’m a cancer geneticist. So with the help of many clinicians around the world we’ve established a very robust melanoma tumour bank which we’ve been using over the years to sequence, using various different sequencing technologies, to identify somatic mutations. So after identifying them we do a lot of statistical and bioinformatic analysis and then finally do functional work to really identify which are the drivers, which are the events that drive melanoma genesis and tumour genesis. So I’ll be talking a bit about that where we’ve identified a few new interesting melanoma drivers as well as looking at how we can use that genetic information to identify new peptides which elicit the immune response in the patient.

What clinical benefits have been seen?

We’ve seen over the years that targeted therapy can be extremely useful and so in melanoma, for example, BRAF, which was identified as an oncogene a while back, finally has a drug that will target it specifically and patients who receive this drug show that the tumours do respond to the drug. Unfortunately there’s resistance that develops after that but we do know that finding the driver events in a tumour can be useful for targeted therapy, so that’s one aspect. Another aspect is that we’ve identified, for example, a new tumour suppressor gene called RAS2 which is involved in inhibiting a very important oncogene called RAS and we know that over 30% of melanoma patients lose the expression of RAS2 and we also know that those patients have reduced survival, significantly reduced survival. So this is a prognostic marker.

Are the proteins that you see when you’re sequencing seen in other cancers?

Some of them are but that doesn’t necessarily mean that they have the same exact function or effect. It’s very important to focus and reanalyse these various different proteins within the context, in the relevant context, so even if they are found to be mutated I would go ahead and functionally analyse it. So we have a very strong emphasis on function. We also develop preclinical models, we use the cell lines that are derived from patients and modify them genetically so that they recapitulate, so that we can use them for genetic screens, for example, or for proteomic screens to really identify the interactions that are found in the various genetic landscapes in melanoma patients. In terms of clinical efficacy the immune system part I described before, it’s really a new method to identify which peptides, neopeptides derived from mutated genes within the melanoma patients, elicit an immune response. So if we’re successful in applying this it may be very useful to detect new antigens in a systematic manner in various different patient samples.

Congratulations on winning the EACR Cancer Research Award – what does this mean for your research?

It gives me a boost, obviously it’s a great honour and really suggests that the direction we’ve taken really does have implications. So I’m very proud of my lab’s works, really the people in the lab and what they’ve been able to achieve over the years.