Unlocking the Next Frontier in Oral Cancer Care

Podcast Transcript

Paul Bryson: Welcome to Head and Neck Innovations, a Cleveland Clinic podcast for medical professionals exploring the latest innovations, discoveries, and surgical advances in otolaryngology - head and neck surgery.

Thanks for joining us for another episode of Head and Neck Innovations. I'm your host, Paul Bryson, Director of the Cleveland Clinic Voice Center. You can follow me on X, formerly Twitter, @PaulCBryson, and you can get the latest updates from Cleveland Clinic Otolaryngology-Head and Neck Surgery by following @CleClinicHNI on X. That's @CleClinicHNI. You can also find us on LinkedIn at Cleveland Clinic Otolaryngology - Head and Neck Surgery, and Instagram at Cleveland Clinic Otolaryngology.

Today I am excited to be joined by returning guest Dr. Natalie Silver. She's the Director of the Head and Neck Cancer Research Program here at Cleveland Clinic. You can follow Dr. Silver on X @NatalieSilverMD. Dr. Silver, welcome back to Head and Neck Innovations.

Natalie Silver: Thank you for having me.

Paul Bryson: For our listeners who maybe haven't had a chance to listen to your previous episode, do you mind starting just by giving some background on yourself, where you're from, how you came to Cleveland Clinic and some of your interests at Cleveland Clinic now that you've established your lab and have quite a bit of momentum here?

Natalie Silver: Yeah, sure. So I trained at Georgetown University. That's where I did my undergraduate education in majoring in biology and Spanish. And then I went on to receive a master's degree in tumor biology at Georgetown University, and then after that graduated went to medical school at Georgetown University, so I'm a three degree Hoya. And then upon completing my medical school, I went to residency at the University of Kentucky in otolaryngology and then did my head and neck fellowship training at the MD Anderson Cancer Center. I did a two year fellowship where one year was focused on head and neck cancer surgery, the ablative or removing the cancer portion of the surgery. And then I did a year of research fellowship under the mentorship of Dr. Jeff Myers, who's the current chair over at MD Anderson Head and Neck Surgery department. And then after that, my first faculty position was at the University of Florida where I was there for five years, and there I served as the disease site group research leader in head and neck. So I dealt a lot with clinical trials in head and neck cancer as well as starting my lab focusing on mRNA vaccine research. And then I was recruited to the Cleveland Clinic, and so I've been here for four years. This is my fourth year and since then I've been working on establishing my lab and as well as treating head and neck cancer patients in Cleveland and beyond.

Paul Bryson: Well, congratulations. We're going to talk a little bit more about some of the exciting things you have going on in the lab and with our medical students. I wanted to ask, Dr. Prendes was on recently, and it sounds like there's been some really cool and interesting developments in oropharyngeal and oral cavity cancer research. Can you share with us some of the things that you're excited about from recent meetings?

Natalie Silver: Sure. I think some of the exciting developments is definitely in the concept of circulating tumor DNA and different ways we can monitor our patients through treatment. There hasn't really been anything that's absolutely changed our practice yet. We're still trying to figure this out with clinical trials, but there is some promising potential applications of this technology, and this is a technology in which we measure specific DNA markers that are representative of a patient's tumor in the blood. So it's a noninvasive way of being able to look at these things and we can track these throughout treatment. And so I think especially for HPV positive oropharyngeal cancer, there's a lot of promise in that arena and for HPV negative cancer, it's a little bit harder, than say oral cavity cancer to find these types of circulating biomarkers for treatment response. But I think that there's a lot of excitement in the field with respect to these technologies.

Paul Bryson: I wanted to give you an opportunity to talk about, I guess my understanding some of your largest thrusts for your lab involved the microbiome as well as a novel head and neck cancer vaccine program. Are you able to share with the listener maybe a status update on what's going on in the lab with both of these endeavors?

Natalie Silver: Yeah, thank you for asking. There's a lot of exciting things going on at both fronts. I think regarding the microbiome, our lab has really been looking deep into the effects of bacteria on head and neck cancer and treatment response. We have a paper currently under review that we're really excited about and hopefully we'll be able to get that out soon so that people can read about our findings. But we believe that we found a biomarker in head and neck cancer that can really help us predict which patients may or may not respond to immunotherapy. We've done a lot of preclinical research using preclinical mirroring models, looking at the effect of bacteria on tumor growth and response to immunotherapy, trying to understand how bacteria potentially, not just that it does have an indication for immunotherapy response, but also why we're really trying to understand the molecular and genetic underpinnings of these traits that we're observing in the lab.

One exciting thing that has happened recently is we received a collaborative Velosano grant with Case Western with investigators there who are experts on both neutrophils and oral bacteria, and we're working together to push forward a phase two clinical trial for oral cancer patients with surgically resectable disease. We are going to be giving antibiotics to these patients prior to surgery, and we are going to be measuring the bacteria found within the tumor among other immune inflammation markers prior to receiving the antibiotic and then at the time of surgery. And we believe that if we lower the bacteria within the tumor, we can also potentially alter the way the immune system is within the tumor, thereby potentially creating a tumor that is more likely to be able to fight cancer or an immune system more favorable for cancer fighting versus suppressing the immune system.

And so that hopefully we will launch that trial in the next couple months. We are getting through the regulatory process right now, but we're really excited about that. Then the other part is the vaccine research. Really excited to say that my group had a recent publication in Cell in which we demonstrated the effects of these personalized mRNA vaccines, which are derived from the patient's tumor. We published our findings in our glioblastoma models, preclinical models, as well as our clinical trial, and we are now finalizing our draft manuscript for the head and neck findings, specifically for head and neck cancer models and patients, and hopefully we will get that out as well. And we are moving forward with vaccine production here at Cleveland Clinic. My chair at the Center of Immunotherapy and Precision Immuno-Oncology Tim Chan has invested in moving this platform forward for patients at Cleveland Clinic, and we've purchased some of the equipment necessary for qualifying and manufacturing the mRNA vaccine here at Cleveland Clinic. We are looking towards the next steps of making this vaccine in a GMP facility in collaboration with Case Western. The ultimate goal is to be able to bring this to patients here and really make personalized vaccines from patients' tumors, and we're actually getting much closer to that. So we're moving forward towards actually rolling this trial out here, which is exciting.

Paul Bryson: Yeah, I mean, congratulations on that. Thanks. I know it is probably a village type of effort…

Natalie Silver: Yes.

Paul Bryson: But it's been awesome to see the types of collaborations that you've built here and the sponsorship and mentorship that you've been able to have while you've been here and then also sort of carry it on with our trainees, other people in the lab. I have a couple questions related to how patients might get involved, but I also wanted to pause and congratulate you on some additional funding success that you've had with our medical students.

I understand there were a couple CORE research grants from the American Head and Neck Society and our American Academy of Otolaryngology-Head and Neck Surgery. Are these grants somewhat related to the work that you're doing that you mentioned with the Velosano grant?

Natalie Silver: Yeah, well, these are definitely related. Radhika Duggal, a very talented CCLCM medical student - that's Cleveland Clinic Learner College of Medicine - she has been working in my lab for the past year and she's been working on mRNA vaccines, kind of working on different iterations of the vaccine. And so she put forward two grants this year for this grant mechanism, which is very competitive. This is a national competition between residents and medical students and others and junior faculty are competing for these awards. And the two awards that she won, one is an mRNA vaccine concept for anaplastic thyroid cancer. We are working with Jeff Knauf, who is an anaplastic thyroid expert here at the Center of Immunotherapy over in the Lerner Research Institute. And in her proposal, we are looking to design a personalized vaccine for these types of patients that often have fatal diseases. And so this is something that was awarded by the American Thyroid Association in conjunction with the American Head and Neck Society. So we're really looking forward to working on modifying the vaccine and combining with other therapies to try to make it the most effective and preclinical models before we propose human clinical trials.

And then the second grant she won is also related to the mRNA vaccine, and that is she's trying to target the vaccine to HPV-positive patients with specific cancer antigens E 67. So designing an optimized vaccine based on that, also using our preclinical models and head and neck cancer cell lines and patient samples prior to designing a human clinical trial. So all the results of her work and these projects will help us inform how we design our future clinical trials once we get our manufacturing processes established.

Paul Bryson: That's fantastic. As we wrap up, can you give us any final take home messages for our listeners, some of which could be patients, what's on the horizon in regards to how patients or other providers might direct patients to the clinical trials that you're talking about or perhaps even contribute to Velosano in some way? It seems like a nice opportunity to continue to support the work that you're doing from sort of the grassroots level and internal funding.

Natalie Silver: Yeah, absolutely. I mean, I think that just saying that Velosano has been a game changer for my lab and my career, I think that the support that they have provided for these projects has really taken my research to that next level has provided and helped me and the foundation for hopefully impactful work that can be disseminated to the community and the scientific community and within patients. And so definitely participating in Velosano, I would encourage that the money will be used very well to support these efforts that are going on at the Cleveland Clinic that are so important and that really means so much to the investigators. Without them, we might not be able to run these types of clinical trials.

Just another thing, I did receive a catalyst award too, which has helped me collect a lot of the bacteria-related data. And so this is another philanthropic award that I am very grateful for, and it takes supporters, patients and other faculty and staff and other caregivers to make these things happen.

And it was very much instrumental in getting my research to where it is. I mean, I don't think I would have the clinical trial ready to go without this type of funding. So I think participating in caregiver catalysts and Velosano supporting the research is great.

And in terms of patients, how they can be involved? Hopefully we will be able to get these trials up and running. And we always are interested in people coming to talk to us about them and visiting us and seeing if they're candidates. And we are striving to really try to improve the care and learn from our patients when they come in, learn about their specific cancer in an individualized fashion. And I think that as we move the field forward, we are going to learn more about what is important. At this point, it's very hard for us to predict how people respond to treatment, and our only real predictor essentially is the HPV status. Aside from that, it's very hard to know who's going to respond to treatment. And so I think that there are things coming along. There are exciting things. I'm biased because I think we're going to, bacteria is a very important factor in this, and it depends how you look at it, how you look at the bacteria. But regardless, I do think that there's a lot of potential strides forward and ways that we can try to tease out these biomarkers in the future and personalize our cancer care.

Paul Bryson: Well, to read more about our latest head and neck cancer research, visit our consult QD website at ConsultQD.ClevelandClinic.org/HeadAndNeck. That's ConsultQD.ClevelandClinic.org/HeadAndNeck. And to speak with one of our specialists or submit a referral, please call our Cancer Answer Line at 866.223.8100. That's 866.223.8100.

Dr. Silver, it's been great to have you on the podcast. Congratulations on all the work that you've been doing and what lies ahead for your lab and for these multiple impactful projects that you're working on. And thanks for joining Head and Neck Innovations.

Natalie Silver: Thank you Paul, appreciate it.

Paul Bryson: Thanks for listening to Head and Neck Innovations. You can find additional podcast episodes on our website clevelandclinic.org/podcasts. Or you can subscribe to the podcast on iTunes, Google Play, Spotify, BuzzSprout, or wherever you listen to podcasts. Don't forget, you can access realtime updates from Cleveland Clinic experts in otolaryngology – head and neck surgery on our Consult QD website at consultqd.clevelandclinic.org/headandneck. Thank you for listening and join us again next time.