Understanding Molecular and Immunological Mechanisms of Acquired Resistance in Cholangiocarcinoma

2 months ago
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With Drs. Katie Kelley of UCSF and Tim Greten of NIH

Cyndi Edwards with the Independent Journalist News Network

The only way to find a cure for cholangiocarcinoma is through research. And that’s exactly what our next guests are doing. Dr. Katie Kelley and Dr. Tim Greten are recipients of a $250,000 innovation grant from the Cholangiocarcinoma Foundation, and they join us now to discuss their work. Dr. Kelley, I’m going to start with you. What are the challenges of treating a rare form of cancer like cholangiocarcinoma, and how is this grant going to help you?

Dr. Katie Kelley of the University of California, San Francisco (UCSF)

So rare cancers and all cancers pose challenges because every patient in and of themselves is an individual with unique factors and details that are critical to deciding the right treatment for them. But when we step back and try to make progress and do research, we need to have enough patients, enough doctors with expertise, enough centers with the critical mass of patients and doctors with expertise, and then an understanding of the specific drivers of an individual cancer, both of response and resistance. One of the challenges specific to biliary tract cancers, including the rare type of cancer we call cholangiocarcinoma, is that they’re exceptionally complex anatomically and biologically. Part of that complexity is that they have an inherent resistance to our own immune systems’ mechanisms of immune control and treatment of the cancer, immune response to cancer. So when we’ve branched out into this renaissance in oncology that we’re experiencing in other tumor types of using our immune system and drugs that harness the immune system to fight cancer, we’re not seeing the same responses in cholangiocarcinoma that we are in many other tumor types.

There turns out to be mechanisms of resistance, perhaps unique to cholangiocarcinoma or unique to some of the other types of cancers that are resistant to immunotherapy. So what we’re trying to do with this grant is coalesce enough patients, enough providers with expertise in this cancer, and enough samples from those patients to be able to study these in a concerted way and identify what are those specific immune mechanisms of resistance that we can then target and help turn the immune system in cholangiocarcinoma patients to a more responsive behavior and allow us to get those deep and durable responses we want.

Cyndi Edwards:

Let’s talk to you, Dr. Greten, about how this is going. Tell me about recent advances that have been made and where you see this research going.

Dr. Tim Greten of the National Institute of Health (NIH):

Yeah, that’s a very interesting question. Let me start out with the entire field of oncology that has really dramatically changed in the past, let’s say, 5 to 10 years with the advent of immunotherapy, number one as well as molecular targeted therapies, and cholangiocarcinoma, as an example for rare cancer, is a perfect example. In this particular indication, we now have cytotoxic chemotherapy that we’ve been using for a number of years, but there are increasing number of reagents that are specifically targeted to molecular changes, which we find in cholangiocarcinoma, IDH mutations, FGFR fusion, just to name a few, as well as immunotherapy that we had just talked about. These treatments have now become standard of care. They are FDA-approved. What we’re currently doing is we’re trying to see if we can improve the outcome and the efficacy of this treatment. But we are also trying to see how we can potentially combine these treatments, and I think those will be dramatic changes hopefully coming up in the next few years.

Cyndi Edwards:

All right. The last question is for both of you, Dr. Kelley, I’ll let you answer first. Why is it so important to collaborate on this type of research?

Dr. Katie Kelley of the University of California, San Francisco (UCSF)

Collaboration is essential, especially for rare cancers like cholangiocarcinoma, and in part, it’s because we need collaboration to build a foundation, like a foundation of a house, to create an infrastructure, to collect samples, to collect ideas, to collect the databases, to pool what are really rare numbers of patients at individual sites into a critical mass that lets us make progress. Whether it’s serum samples, tissue samples, or cell lines that we can study in mice, we need a network, and we need a foundation like Cholangiocarcinoma Foundation’s support to help build that network for communication as well as logistical shepherding of samples and data between multiple sites.

Cyndi Edwards:

Dr. Greten?

Dr. Tim Greten of the National Institute of Health (NIH):

Yes. Let me add, even if this is a rare cancer, there are still many different aspects that we study in cancers, and that’s why it is so important to collaborate because different investigators and specialists have different expertise. Some are more clinical, some are more preclinical, some have more expertise in molecular medicine, more in technology, and getting here, different experts with a different perspective, I think, is pivotal to advance the field.

Cyndi Edwards:

All right, Dr. Katie Kelley, Dr. Tim Greten, thank you both very much, and good luck with your research.

Dr. Tim Greten of the National Institute of Health (NIH):

Thank you.

Dr. Katie Kelley of the University of California, San Francisco (UCSF)

Thank you.

Cyndi Edwards:

Thank you for tuning in. We’ll see you again next time. Bye-bye.

Cyndi Edwards is an Independent Journalist contributing to the Independent Journalist New Network

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