Molecular profiling explained by Dr David Spetzler: An interview

Molecular profiling explained by Dr David Spetzler: An interview

NH: Hello and thank you for tuning into the program. I’m your host Neil Howard here on Health Professional Radio. Our guest today is Chief Scientific Officer at Caris Life Sciences, joining us here today to talk about his company’s involvement with several studies where cancer is being treated based on its molecular profile rather than its site of origin. Dr David Spetzler, thank you so much for joining us today.

DS: Thank you for having me.

NH: Now as Chief Scientific Officer at Caris Life Sciences, give us a bit of background about yourself and then talk about what Caris is involved in, as that involvement relates to cancer research.

DS: Sure. So my background is in mathematics and molecular cellular biologies. I joined Caris about eight years ago working in the research department. Our mission is to develop cutting edge molecular diagnostic assays for the detection and characterisation of cancer. Our primary focus is on ascertaining which drugs patients are going to most benefit from, and simultaneously identify drugs that patients will not likely benefit from.

So cancer is very much a disease of the molecular pathway. And what we’ve found over the last decade of research really is that while certain aberrations within pathways are more common in particular lineages, really those alterations transcend lineages. So that functionally manifests itself in approvals like recently happened for Keytruda [pembrolizumab] and MSI unstable patients, where a particular patient may harbour an underlying alteration that makes them eligible for a drug that would not typically be given to that type of patient.

So the development of the science is really quite fast and we’re seeing enormous acceleration in these types of approvals and applications. Some key examples are the NCI-MATCH study that’s going on right now as well as the ASCO TAPUR study, in terms of really proving out this pan-lineage hypothesis for the treatment of cancer patients.

NH: So how do you actually determine what type of patients exist for these types of drugs?

DS: So what we do is apply a multitude of different technologies to basically any cancer patient that is receiving our service. We will test any solid cancer patient and we will look at DNA mutations, we will look at alterations in the RNA and the transcription element, and we will look at alterations in the protein level expression. By taking that technology agnostic approach, we are really maximising our ability to identify what is driving that particular patient’s cancer. And so it could be that it’s a change in protein expression like PD-L1, which would enable patients to receive checkpoint inhibitors, or it could be a translocation event like NTRK, which has recently seen some pretty promising data presented at ASCO.

Really a lot of these alterations are quite rare so the best way to tackle the problem is to do a broad set of underlying markers, to really understand that particular cancer’s patient. The way that we’ll really tackle this, I believe, is with broad-based profiling where the percentage of patients that harbour any one particular mutation are small, but our ability to intervene on lots of different mutations is increasing quite rapidly. So we will be able to influence and help ever increasing percentages of patients.

NH: Is there are type of patient or cancer that seems to show itself more than any other, thereby not classifying it as a rare cancer, or do you only deal with rare cancers or any type of cancer?

DS: Really it’s any type of cancer. We focus primarily on metastatic disease. For early stage cancers, surgery is by far the most effective intervention, but once you get to the point of utilisation of chemotherapies once surgery has essentially been exhausted, that’s when molecular profiling is really pertinent. In terms of types of cancers that are more commonly helped by this approach, lung cancer is probably seeing the fastest approval rating for new therapeutic interventions.

There is a multitude of markers now that should really be done right at the get-go for metastatic cancer patients. You know, many of them have been around for quite a while, so EGFR, KRAS1 have been around for quite a while, but we’re really now seeing the emergence of PD-L1, NTRK is likely to be approved soon, BRAF just received an approval. So a lot of work is being done in this camp, and really it’s good for society as well because it’s very costly to give cancer patients drugs that are ineffective. And so not only is there significant benefit to the patient, but this is an approach that will help control costs for our society as well.

NH: Are there ever any instances where a patient’s treatments can be changed mid-therapy based on new evidence about that patient due to this technology, or once they’re in treatment is it pretty much a done deal and they finish the treatment, or either start this from the get-go as you say or don’t start it at all?

DS: So as you’re changing lines of therapy, that’s typically where it happens. In terms of monitoring within a particular cycle, that’s less common. The data is still emerging there, but for example you can look at patients that are receiving a TKI (a tyrosine kinase inhibitor) and if they are seen to demonstrate the emergence of resistant mutations, then they’re likely to have a therapeutic change sooner rather than waiting for disease progression to initiate that change, to get ahead of it. But that’s still pretty forward thinking, it’s not standard of care yet.

NH: Is there any age factors that play a role as far as accuracy when it comes to this molecular type of testing?

DS: No. It’s really applicable to any age of patient. We see it applied to younger patients typically more often than older patients, and that’s likely just due to the fact that if you’re young and you develop cancer, it’s typically a pretty aggressive disease. So physicians are looking for as many opportunities to combat it as possible.

NH: Now is there a place that our listeners can go online and get more information about this Keytruda approval?

DS: Certainly, I mean the FDA has information and then there are a multitude of different websites popping up. Of course www.carislifesciences.com is also a resource for that type of information.

NH: Well, I appreciate the information and thanks for taking the time today, Dr David Spetzler, thank you so much for coming in.

DS: Thank you.

NH: You’ve been listening to Health Professional Radio. I’m your host, Neil Howard with Chief Scientific Officer at Caris Life Sciences. Transcripts and audio of this program are available at healthprofessionalradio.com.au and also at HPR.fm. You can subscribe to this podcast on iTunes, listen in and download at Soundcloud, and be sure to visit our affiliates page when you visit our platform at HPR.fm and healthprofessionalradio.com.au.

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