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Precision Medicine: Targeted Treatment for Lung Cancer

(upbeat music) – Good morning. My name is Konstantin Dragnev and I’m a counselor researcher and a medical Oncologist. I treat patients with lung cancer and I do research on lung cancer. And over the past, probably 10 15 years, we’ve made significant progress in our understanding of lung cancer. Now it is not a single disease. It is a group of multiple distinct subtypes of cancer that have specific molecular features, specific … Different cause, the prognosis is different and the treatments are also different. We’re now beginning to find treatments that we can tailor to the individual patient. Rather than treating everybody the same. And when we have a target that we have identified, we have the treatment. The outcomes are much better.

Patients live significantly longer and with much better quality of life than when we use traditional chemotherapy. And to put things in perspective, patients with advanced lung cancer who do not receive treatment their median time is about six months. Patients with the same advanced lung cancer, if they have one of the molecular sub types of the disease and receive targeted treatment, they live two three four years. Yes this is not cure but it’s a significant progress. Identifying the different types of lung cancer has become now standard in most places and here at Dartmouth, when a patient is identified with lung cancer their tumors are analyzed for many genetic changes before treatment is selected.

So that when we meet and we have to make a decision, it is based on the specific features of their cancer not cancer in general. There are many genes that are important for lung cancers and for some of these we have treatment for many treatments are being designed. And sadly, probably the most common genetic change, the most common mutation in lung cancer.

This is a mutation of an oncogene called kras. It has eluded effective treatment. In my research and kind of in my clinical practice, I’m focusing on finding better treatments for that specific subset of lung cancers with Kras mutations. And my work in the laboratory established a way that derivative of Vitamin A, Retinoids, Rexinoids. They can suppress lung cancer by focusing on a specific molecule that is important for the growth of cancer cells. It’s called Cyclin D1. It is a molecule important for the cell cycle, how cancer cells grow. And we uncovered the mechanism, how Vitamin A analogs can destroy that target Cyclin D1. The technical term is Induced Proteasomal Degradation, but that is what it mean. The molecules get destroyed. And we found that combining a Vitamin A analog with an existing targeted treatment such as an EGFR inhibitor, enhances the suppression of Cyclin D1 of the target and this is associated with significant blockage of the growth of cancer cells.

So based on these preclinical results, I conducted and completed three translational clinical trials here at Dartmouth, studying the combination in patients with lung cancer who have become resistant to standard treatments. We saw improved benefits. Patients were living longer, with much better quality of life than when treated with chemotherapy. And interestingly, the treatment was work better for patients with that specific mutation Kras. And right now I’m conducting a trial with the next generation of this combination. And this is one approach where you’re indirectly focusing on the target cyclin D1. I’m trying to degrade it. In parallel I’m working on a clinical trial with a drug that directly blocks cycling D1. it blocks an enzyme that stimulates, activates Cyclin D1. It’s called Cyclin Dependent kinase 4/6 or CDK 4/6 for sure.

We completed the trial, it was a multicenter trial. We showed kind of enhanced benefits for at least some subsets of patients with lung cancer that carry Kras in their tumor. That have become resistant to prior treatment. So an unfavorable prognosis. And currently our research really focuses on identifying what additional genetic changes, what additional targets may be involved so that we can find treatments to enhance the activity of the combination. And with continued support, this research is going to lead to better results for our patients and this is why we do cancer research.

Thank you. – Dr. Dragnev your research sounds exciting and clearly it’s important. You’re obviously enthusiastic about it. Now we often hear the term Precision Medicine and Precision Medicine is particularly relevant to cancer research. And really what you’re talking about is targeted treatment for specific types of lung cancer. So is your study an example and a good example of targeted therapy or if we will, Precision Medicine for these Kras, which is the subtype of lung cancer you’re speaking about? – We’re talking about the same thing, Precision Medicine, targeted treatment, individualizing the therapy for the patient in front of you.

This is all what I believe the future of medicine is and I’m enthusiastic. This is how we’re going to improve the results by focusing on their specific features. – So Dr. Dragnev if you could articulate your vision for success beyond what you’re doing here at Dartmouth Hitchcock, what would that be? – I am a lung cancer researcher, but the mechanisms that are being identified, the targeted treatments that are being developed, they are applicable to a much broader population. And once we identify a pathway that’s important for lung cancer, similar pathways are important for other cancers. So I think that the concept of Precision Medicine goes across the different tumor types and I will be happy if we see better results in lung cancer, but I will be even happier if these benefits go across different cancers.

Eventually leading to most effective treatments for all the patients that come to Dartmouth Hitchcock. – So the work is clearly important. And you’ve really had tremendous success so far, but if you had more support for your research, what would it lead to? – The type of research that we do requires a lot of resources and if I have more support I will be able to first look at more potential targets for treatments and then accelerate the pace of translation of what we see in the lab into clinical treatments for patients with lung cancer because I’m interested in lung cancer, but it can go beyond patients with lung cancer. I would like to develop treatments for patients who come to Dartmouth, but if effective, these treatments can be accessible to patients anywhere. – Doctor Dragnev, thank you very much. We really appreciated your time today and we now understand much better what your goals are and we thank you very much for sharing those with us today.

– Thank you for having me. .