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ROS-1 Rearrangements: What Are They?

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GRACE Cancer Video Library - Lung

GCVL_LU-BA03_ROS-1_Rearrangements_Defined

 

Dr. Ross Camidge, University of Colorado, describes ROS-1 rearrangements and compares them to ALK rearrangements in frequency of occurrence and response to treatment.

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ROS-1 rearrangements are like the sister to ALK gene rearrangements. They’re also a gene which is silenced in most adult tissues, which is turned on again by a gene rearrangement creating what’s called a fusion protein which can drive the cancer cell. Structurally they’re very similar to ALK rearrangements and they respond to many of the same drugs. Particularly crizotinib, the first licensed ALK inhibitor, has also clearly shown good activity in ROS-1 driven cancers.

They’re rarer, maybe one quarter as common as ALK rearrangements or less. There are subtle differences. The benefit of crizotinib in ROS-1 gene rearranged lung cancer actually seems greater than it is in ALK, so the response rate is 70% as opposed to 60%. The median progression-free survival, the time it takes for the cancer to grow, on average is about 19 months as opposed to nine or ten months with ALK.

People are wondering about why the difference is, and there are various theories. Maybe crizotinib is actually a better ROS-1 inhibitor than it is an ALK inhibitor. Maybe the frequency of progression within the brain, which we know is somewhat of an Achilles heel for crizotinib and ALK-positive lung cancer — maybe that’s not such an issue with the ROS-1 rearranged patients simply because they have a lower frequency of deposits in the brain. Increasingly on a biological level, we’ve also seen a little bit of data that ROS-1 may be a more genetically simple cancer that ALK. It occurs in a part of the genome, part of the DNA of the cell, which is more structurally stable, so its ability to mutate and evolve in the presence of the drug and then progress later may be less. Either way, it’s a good thing to have if you have it.


GRACE Video

What is the Value of Testing for Molecular Markers in Advanced NSCLC?

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GRACE Cancer Video Library - Lung

GCVL_LU_Testing_Value_Molecular_Markers_Advanced_NSCLC

 

Memorial Sloan-Kettering Cancer Center medical oncologist Dr. Greg Riely explains how testing for specific mutations in patients with advanced NSCLC can guide prognosis and treatment recommendations.

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When we’re evaluating a patient with lung cancer, the first question we start to ask is, what’s going on with this patient’s cancer? Where is the disease, so has it spread to other sites, and what does it look like under the microscope? So, what’s the tumor histology, is it an adenocarcinoma, squamous cell carcinoma. And then, importantly, molecular testing has become a critical part of our understanding of a patient with lung cancer.

Now, by doing molecular testing, we’re able to better refine the prognostic and predictive value of a variety of drugs and treatments that we have going forward, for designing an overall treatment plan for a patient. Some of the most common testing that should be done are EGFR and ALK — now, these are important because these both have FDA approved drugs that are indicated for abnormalities in EGFR and ALK. If you go beyond those two things, there are actually a long list of drugs that can target individual molecular aberrations and molecular abnormalities, but they’re uncommon, and we don’t have FDA approved drugs for those things, but I think if we go beyond those EGFR and ALK tests, we can learn a lot more and sometimes help patients a great deal.


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Dr. Bob Doebele on the Most Promising Upcoming New Targeted Agents and Molecular Pathways for Lung Cancer Treatment

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Dr. Bob Doebele from the University of Colorado, provides his view on the targeted therapy approaches most likely to become clinically useful in lung cancer over the next several years.


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Dr. Geoffrey Oxnard on the Most Promising Upcoming New Targeted Agents and Molecular Pathways for Lung Cancer Treatment

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Dr. Geoffrey Oxnard, Dana Farber Cancer Institute, provides his view on the targeted therapy approaches most likely to become clinically useful in lung cancer over the next several years.


GRACE Video

Dr. Karen Kelly on the Most Promising Upcoming New Targeted Agents and Molecular Pathways for Lung Cancer Treatment

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Dr. Karen Kelly of the University of California, Davis, provides her view on the targeted therapy approaches most likely to become clinically useful in lung cancer over the next several years.


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