Tag Archive for: hedgehog pathway

Treating Non-Melanoma Skin Cancer With Targeted Therapies

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Treating Non-Melanoma Skin Cancer With Targeted Therapies from Patient Empowerment Network on Vimeo.

Dr. Anna Pavlick discusses targeted therapy, specifically hedgehog inhibitors for basal cell cancers, explaining how these therapies block cancer growth pathways, their rapid effectiveness, and potential side effects.

Dr. Anna Pavlick is a medical oncologist and the founding Director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. Learn more about Dr. Pavlick.

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Transcript:

Katherine:

How do targeted treatments to treat non-melanoma skin cancer?  

Dr. Pavlick:

Targeted therapies are approved for basal cell cancers in particular. They are certainly not for squamous cell or Merkel cell, but basal cell because basal cell cancers use a pathway called the patched and the smoothened pathway to multiply and metastasize or spread to other parts or just continue to grow.

And hedgehog inhibitors will inhibit that or block that particular pathway. These pathways are so highly overexpressed in basal cell cancers that we don’t even need to check when we do a biopsy. We don’t routinely check and send the biopsy to see if these tumors have those pathway alterations because 99.9 percent of them do. 

And so, we can easily give this targeted therapy to a patient with basal cell cancer. The nice thing about giving a targeted therapy is like shutting off a light switch. If the light is on and the cancer is using this pathway, if you shut the switch or block that pathway, things get better very, very quickly. Part of the downside to some of these hedgehog inhibitors are some of the side effects. Because basal cell cancers occur in older populations, these are patients that may in fact be sicker or more frail. And two of the side effects that can occur from hedgehog inhibitors is alteration in taste and the feeling that you’re just not hungry. 

So, anorexia and if you’ve got a thin frail patient and now you give them something that’s going to deter them from eating even more, they may be problematic. And not everybody gets those, but those are the most concerning. Patients do have a chance of having hair thinning or hair loss with hedgehog inhibitors. Another reason why many people just will say to me, “I don’t want them even though it will respond faster. I’d rather be treated with immunotherapy because then I’m not going to lose my hair.” And for a lot of women no matter what your age is, hair is an important part of who you are.  

Katherine:

Yeah.  

Dr. Pavlick:

And the last other significant side effect of hedgehog inhibitors is muscle cramps. And many times, this will happen in the middle of the night. People get really bad charley horses. 

I have patients who say they get cramps in their fingers or cramps in their hands. It’s not as easy to manage. We do know that sometimes by giving patients a medicine called amlodipine which is commonly used for blood pressure, this may help resolve or reduce the number of cramps they get, but it doesn’t work for everybody.

And so, you kind of have to balance out how quickly do you need this cancer to go away or respond? Because if you do use a hedgehog inhibitor, you’re going to get a very rapid response. If you use immunotherapy, just think about it. You’ve got to wake up your body’s immune system. You’ve got to get those T cells to get moving. And so, responses are not going to be in a matter of days. It’s going to more in a matter of weeks. With the hedgehogs, your responses are seen in a matter of days. 

Katherine:

Wow. So, sometimes, it could be a difficult decision to make?  

Dr. Pavlick:

Yeah, you have to weigh out pros and cons. Sometimes, you have patients who can’t swallow pills. Well, if you can’t swallow a pill, then a hedgehog inhibitor is not on your list of things that you can take. And to the contrary, some people are just really averse to having to come in and get an infusion because they may have needle phobia or they just don’t want an IV infusion. And then a hedgehog inhibitor is your first line of therapy.  

Advanced Non-Melanoma Skin Cancer Test Results | Understanding YOUR Disease

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Advanced Non-Melanoma Skin Cancer Test Results | Understanding YOUR Disease from Patient Empowerment Network on Vimeo.

What should advanced non-melanoma skin cancer patients know about test results? Dr. Soo Park explains the types of skin cancer tests and reviews questions you can ask your healthcare team to help better understand test results. 

Dr. Soo Park is a Medical Oncologist at Moores Cancer Center at UC San Diego Health. Learn more about Dr. Park.

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Katherine:

So, once a patient has been diagnosed, what are the tests that help understand more about the patient’s individual disease?  

Dr. Park:

So, it’s always important to get a biopsy, so then we can tell which type of non-melanoma skin cancer it is. 

And that’s when we look at your cancer under the microscope, and a special doctor called a pathologist. And actually, they’re also really important as part of our multidisciplinary team. They look at the tumor under the microscope, and they help us decide and tell us which type of non-melanoma skin cancer it is. 

But aside from that, I think imaging is really important. So, that are things like CT scans, MRI scans. Sometimes we have to also recommend a PET scan, which is another type of special scan. And these images are really to help us look deeper into the structure of your body, because I can only see so much from the outside.  

And they can really help us tell how deep is the cancer; is the cancer around any critical structures? Is it anywhere else in the body? Because if we find cancer far away from where it originally occurred, that may tell us that the cancer is a later stage.  

Katherine:

So, let’s just go with a scenario. Somebody comes in to you, and they have a lesion on their cheek, for instance.   

Would you do a whole body MRI or a CT scan to see if that…once you’ve done a biopsy, you find that it’s cancerous. Would you do a whole body MRI, or a scan of some sort, to see if the cancer was anywhere else?  

Dr. Park:

So, we typically don’t, because we know the patterns that – for instance, like you mentioned, like a skin cancer in your cheek can go to. And so, non-melanoma skin cancers on the face or anywhere in the body, they typically like to go to the lymph nodes that drain that area. And so, if you have a lesion on your face, that’s typically your neck.   

And so, we’ll do a good exam of your face, your neck, but we will also get imaging of those areas. So, we typically get an imaging focused on the head and neck. If we find something abnormal there, then that may tell us we need additional imaging in the other parts of the body. But more often than not, we don’t start with a whole body scan.  

Katherine:

Okay. What questions should patients ask about their test results?  

Dr. Park:

So, I think patients should definitely ask, “What type of skin cancer do I have? How did it arise? Where all in my body is the skin cancer? What does my blood work look like?” And I think patients should also be aware that for many years now, we send tumor samples for something called molecular sequencing, and that just tells us different types of mutations that may be in your tumor. And that’s really important, because there are some drugs we have now that are only for patients that have specific mutations in their tumor.  

And so, if you are one of those patients that has a specific mutation, that opens the door to another type of therapy for you. And, you know, that’s something that’s now recommended, actually, by a lot of cancer societies, to really send your tumor for some type of molecular sequencing, so we can level the playing field for all patients, and offer them the full range of treatments that we have.  

Katherine:

Yeah. What are the common mutations?  

Dr. Park:

So, for basal cell skin cancer, almost all basal cell skin cancers are driven by abnormality in a certain pathway called the hedgehog pathway. Yeah, I’m – 

Katherine:

Interesting. Why? 

Dr. Park:

It was named, I think, by someone. All these names are people by someone that discovered it, and they get the rights to name the pathway. But for a basal cell, it’s the hedgehog pathway. And so, in the hedgehog pathway, there are certain types of mutations specifically associated with that pathway. And one of them, among these mutations, we look for drugs that can inhibit this pathway. So, there are drugs that specifically target the hedgehog pathway.  

They’re called hedgehog inhibitors, and they’re oral medications or pills that you can take every day. And those are for patients with basal cell skin cancer, because the basal cell skin cancer came about because the hedgehog pathway is not normal. But for squamous cell skin cancer, squamous cell skin cancer often has a lot of mutations. And unfortunately, they’re the type of mutations that we actually don’t have a drug for at this moment. But one unique thing about squamous cell skin cancer is that it has so many mutations.  

And so, that means that it has a better chance of responding to a different type of treatment. It’s an IV treatment known as immunotherapy. And so, that’s something that’s relatively recent, I think, in the past five years now. We’ve started using immunotherapy for patients that have squamous cells skin cancer, and it’s worked remarkably well.