Harnessing Precision Medicine in Oncology With Ofer Sharon, MD

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In this interview, Ofer Sharon, MD, the CEO of OncoHost, explains the unique opportunities for harnessing precision medicine in oncology, the unmet needs regarding biomarker development, and the potential of utilizing a multicomponent biomarker approach for understanding the mechanisms of therapy resistance and developing novel pathways for treatment.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. I'm Keira Smith, and today I'm joined by Dr. Ofer Sharon. Thanks so much for coming on today.

Ofer Sharon, MD: Thanks for having me. It's a pleasure to be here.

Oncology Data Advisor: To start off, would you like to introduce yourself and then share a little bit about OncoHost as well?

Dr. Sharon: Of course, I'd be happy to. I'm Ofer, and I'm the CEO of OncoHost. I am a Physician by training. I'm an Internist, but I've spent most of my career in the industry founding companies. I like the intersection between mathematics, algorithms, and medical applications. So, I have three companies in this field, OncoHost is my latest and favorite baby, and we are dealing with precision medicine. We're dealing with precision medicine with a very, I would say, unique approach compared to what's out there in the market or in clinical development. We're trying to get a very holistic picture of this interaction between the patient, the tumor, and the therapy, in order to better understand resistance mechanisms and help physicians to guide therapy or find the optimal therapy for the patient.

Oncology Data Advisor: For a little bit of background, what exactly is precision medicine, and what is precision oncology in particular?

Dr. Sharon: That's a great question. I mean, we can spend hours talking about the answer to this question, but to put it very, very simply, I think that we've been very much focused, when we're thinking about drug development, on finding drugs that will treat as many patients as possible. This approach took us a long way in many indications, also in cancer, but it seems like in recent years, we reached a plateau in terms of our ability to improve clinical efficacy when we look at the entire population. Yet we do identify patients who some are calling "super responders." You treat the patients, and even metastatic cancer disappears.

I think that we've reached a realization in the last 15 years. I think it's being boosted lately, but we are talking about a process where we understand that if you want to jump to the next stage in terms of cancer treatment efficacy—not only cancer, we are focusing in this discussion on cancer, but I don't think there's a difference between precision medicine and precision oncology in that sense—but if you want to go to the next jump, we should try to better understand the patients, because obviously there's a difference. There's a difference between a cancer patient who is an 85-year-old woman and a patient who is a 45-year-old man. I think it's clear to all of us that this is not the same human being. We can't expect those two persons to respond the same way to therapy, yet because of the way clinical trials are designed, because of the way drugs are designed, they are most likely to be treated the same way with one-size-fits-all protocols.

Precision medicine is here to make the next jump, and that is to try to find patients or treat patients according to a much better understanding of the complexities of the biology, the difference in biology between human beings, which are there. It's obvious that the differences are there, but we need to be able to measure them, and I think that we will reach a stage where we can actually do that.

Oncology Data Advisor: Thank you, that was a really great overview. What are some of the unmet needs regarding biomarker development in precision oncology?

Dr. Sharon: Yes, it's actually very interesting. I can share a slide that demonstrates it really nicely if you want, and this tells the entire story. As we speak today, there are over 6,000 clinical trials looking at different immunotherapies, different combinations of immunotherapy with other therapies, in different cancers. 6,000 clinical trials. Unfortunately, most of those will fail and will never reach the clinic. And if we look at the cancer landscape, as you can see on the right-hand side of the slide, we can see that basically every cancer type is treated, or is going to be treated, with immunotherapy in this case.

The thing is, that we don't have good biomarkers for immunotherapy.

So how, as a clinician, am I supposed to make a choice between this treatment or the other treatment? And this is where biomarkers are needed—we need to be able to understand which patient will benefit from which treatment. This is super important, because, especially in cancer and especially in the more advanced stages of cancer, patients don't have time to waste. There was a recent publication that said that a delay of four weeks in treatment may reduce overall survival by five months, which is a lot. We don't have time to waste, and we want to find the best treatment or the optimal treatment for the patients.

And believe it or not, for the entire field of immunotherapy today, we almost have no biomarkers. We have one approved biomarker, which is called programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1). Another biomarker that is relevant to a very small subgroup of patients is tumor mutational burden (TMB). And those two biomarkers, by the way, are not accurate biomarkers. They're not predictive biomarkers; they may be prognostic biomarkers. Basically, we have a lot of options to treat with, a lot of clinical trials that are being run as we speak to identify more treatments, but biomarkers are lagging far behind. So, this is where the need is coming from.

Oncology Data Advisor: Thank you, that was really helpful in understanding. In your article you wrote recently, you mentioned a multicomponent biomarker approach. What does this approach involve, and how does this aid in diagnosis and treatment selection?

Dr. Sharon: This also requires some kind of background, but the way we usually think in traditional Western medicine is that we're trying to find an association between a cause and effect. I have pneumonia because of these bacteria or this viral infection. I have a disease because of this mechanism. If we think that way, we can actually look for treatments that are targeting those specific causes of disease. And the approach is similar in cancer. Think about it. I have this mutation. I will try to target this mutation in order to treat the cancer, and this approach proved successful. But again, as I said earlier, we reached a plateau; we reached a point where we were not improving further.

When you look at two patients who took exactly the same treatment, and one is responding and the other is not, in order to identify the cause and the reason why one is responding and one is not, looking at one specific protein or one specific mutation is usually not enough. Because biology is much more complex than that. And immunotherapy is a great example. Immunotherapy holds great progress in oncology, and the mechanism of action of immunotherapy almost by definition is not cancer-specific but targeting the immune system. So, you would expect to see treatments that are almost universal in terms of efficacy, but we see that they are not. The reason they are not, is because, again, the immune system is complex. It's a complex system. Many cells are involved, many proteins are involved, many signaling pathways are involved, and it's very hard, almost impossible, to find one component in this very complicated system, the immune system, that will tell us a story about the resistance, that will tell us a story about the ability of the patient to respond to the therapy.

This is why when we are looking at immunotherapies, for example, what we need to do is take a very holistic approach. Try to understand not one component, not one single protein. Try to understand the story. Which resistance mechanisms are involved, which genes are involved, which pathways are involved? One good comparison that Professor David Carbone gives in his lectures, is that when you're looking at specific mutations or genes for targeted therapies, it's almost like a switch, on or off. It's either there or not. When you're looking at the immune system, you are looking at so many cells and so many signaling pathways that you just cannot identify the switch. It's almost like a pilot switchboard. You have a lot of data points, a lot of information that you need to take into consideration in order to look for a good predictive biomarker. And this is what the multicomponent approach involves—looking at different proteins, different signaling pathways, and sometimes combinations of proteins with clinical characteristics of the patients in order to get a much better picture.

Oncology Data Advisor: What research is OncoHost conducting to evaluate and integrate multicomponent biomarkers into clinical workflow?

Dr. Sharon: What we are doing at OncoHost—and I think this is very unique to the company—is we are trying to identify proteins that are differentially expressed between responders and non-responders. And I'm not talking about one protein—I'm talking about hundreds of proteins, because some of those proteins may be overexpressed in one patient and others may be overexpressed in other patients. But when you look at the larger number of proteins, it is more likely, as evidenced by our clinical results, that you will find those proteins that indeed are related to the resistance. So, we're looking at groups of proteins, we're looking at groups of signaling pathways. We are focusing on five major resistance mechanisms that are the target of a lot of clinical research and new drugs.

By doing that, basically we are shying away from this search for a single protein or a single biomarker, but rather looking at large pieces of information coming from different biological processes. I always compare it to space. Asking two spaceships to meet in space without a map is almost impossible. Space is so big that the odds that those two dots will connect are very, very low. But if you're looking at clouds of processes, the likelihood of finding some interaction is higher, and this is exactly the multicomponent approach. Let's try to understand which signaling pathways, not necessarily single proteins, are overexpressed in different patients, and by doing that, we'll be able to extrapolate and better understand the resistance mechanism that caused the patient not to respond to therapy.

Oncology Data Advisor: That's a really helpful analogy in understanding.

Dr. Sharon: We are now starting an additional clinical trial. Up until now, I spoke about proteins, but proteins are not giving us the whole picture. By the way, this is why mathematics is so important here, because there's almost no way to digest those amounts of data and find patterns of behavior without using advanced mathematics. But the new research that we are going to start soon is going to combine proteomics with DNA analysis, with the microbiome, with immune cell activity. It's a very extensive clinical trial which is going to give us a very deep understanding of the resistance and the development of resistance of cancer to therapy over time.

Oncology Data Advisor. That's great. Anything else or any parting thoughts you'd like to share about your work in this field?

Ofer Sharon: I would just say that we're very passionate about what we do, the team here at OncoHost, and I think the entire field. I think that precision medicine is going to be the next major leap in cancer therapy, and I'm looking forward to being part of the story.

Oncology Data Advisor: Absolutely. Well, thank you so much talking about all this today. It was great to hear about, and I look forward to hearing more as well.

Dr. Sharon: Perfect. Thanks for having me.

About Dr. Sharon

Ofer Sharon, MD, is a Physician and Entrepreneur with more than 20 years of experience in clinical and commercial product development for health tech, biotech, and medical device industry startup companies. He is the CEO of OncoHost and has co-founded several other health care companies focused on precision medicine, bioinformatics, and machine learning in medicine.

For More Information

OncoHost (2023). Available at: https://oncohost.com/

Sharon O (2023). A multicomponent biomarker approach will shift cancer care. OncoZine. DOI:10.14229/onco.2023.06.12.010

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.