Unexpected role for Immuno-oncology in SCCOHT

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Published: 12 Jul 2018
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Dr Douglas Levine - NYU Langone Medical Center, New York, USA

Dr Levine speaks with ecancer at BCGS 2018 about small cell carcinoma of the ovary - hypercalcemic type, a rare disease with low trial support.

He discusses the discovery of a single gene responsible for the disease, and how this is impacting the development of treatment with immune agents and cell-cycle regulators.

Dr Levine also spoke with ecancer about lowgrade serous carcinoma, here.

We had a symposium today on small cell carcinoma of the ovary hypercalcemic type. It was an international symposium of all people around the world who study this disease. It’s a cancer that’s very, very rare and it affects young women and young adults and it’s very aggressive. A number of years ago myself and a few other groups discovered the gene that causes the cancer, it’s a gene called SMARCA4. We’re now developing some therapeutic options to help treat this cancer which is otherwise quite difficult to treat.

What options are being developed?

Right now we’ve had some good success with immunotherapy. We have a number of patients who have responded very nicely to immunotherapy and we’re trying to work out the mechanisms by which immunotherapy works in these particular cancers. Most immunotherapy works in cancers that have a lot of DNA mutations; in this particular cancer there’s only one mutation in one gene so it’s called a monogenic disorder. That’s unusual for immunotherapy to work and so we’re trying to figure out why that actually happens.

Other treatments that are being worked on are treatments that affect the cell cycle and some folks from McGill presented some very interesting data on using palbociclib, which is a CDK4/6 inhibitor. Other people are working on epigenetic regulators to treat this cancer.

Are you suing immunotherapies that have had success in other areas?

We’re using the standard immunotherapies – pembrolizumab, nivolumab. We’re also trying to get a clinical trial working and we’re going to be talking to multiple companies because Merck and BMS have not decided to support this trial because it’s a very rare tumour and it’s always hard to do rare tumour research because you can never really say ahead of time that we’re absolutely going to get hundreds of patients on the study when there are only hundreds of patients around the world who get this very rare cancer. So we’re trying to develop a phase II trial to study immunotherapy in this disease.

Any final thoughts?

We’re trying to figure out what part of the immune system is really accounting for this type of response. We’re also working on the epidemiology, trying to figure out what the actual incidence is and developing patient registries. Also a very important part of the disease is that a fraction of the cancers can be inherited and so probably 10-40% of the cancers can be inherited obviously from parents. So genetic counselling and genetic testing is a very important part of treating the cancers.