Article: Transcript: Targeting K-RAS in Lung Cancer is a Goliath Task (But We Have Some Answers) - Jia Luo, MD @Jia_Luo @DanaFarber @harvardmed #ASCO22 #OncoTwitter


Transcript: Hi there my name is Jia Luo I'm a thoracic medical oncologist at Dana-Farber it's very nice to speak to you today about my talk at ASCO called Taking on Goliath Targeting K-RAS and lung cancer so the meaning behind Goliath here is that it is a deeply difficult question but we've made a ton of headway and i think we need to take advantage of the momentum we've made in the field to keep advancing it forward so my overall take home from this talk is that K-RAS lung cancer is common and an important question we have our first fda approved treatment and there are many clinical trials up ahead that will continue to develop new treatments for both K-RAS G12C lung cancer and other subsets of K-RAS lung cancers so to summarize my talk overall the first point i want to emphasize is that K-RAS lung cancer is actually the most common form of oncogene driven non-small cell lung cancer it's more common than EGFR

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here in the united states it accounts for 25 percent of individuals with non-small cell lung cancer and is about 50 000 individuals in the united states per year alone additionally we think that it's a unique subtype of non-small cell lung cancer those with K-RAS driven non-small cell lung cancers tend to have a higher tumor mutation burden that's thought to be due to the carcinogenesis from tobacco exposure and they tend to have a these c to a transversion mutations that drive the high tumor mutation burden additionally the tumor microenvironment of these tumors tend to have more immune infiltrated cells when we examine this by immunohistochemistry or multiplex immunofluorescence and unexpectedly unsurprisingly these individuals tend to benefit from immunotherapy-based treatment because of these features and so the subset analyses of phase three studies of the registration trials involving checkpoint inhibitors in the first line if you look at the K-RAS mutant subset you'll see that those individuals who receive either immunotherapy or immunotherapy and chemotherapy versus those who receive chemotherapy tend to benefit from the immunotherapy-based treatments so this K-RAS lung cancer is a is a distinct subtype and we're also learning that each allele such as G12C which is the most common is a slightly different type of K-RAS lung cancer so in the talk i will go more in depth about why it took so long 30 plus years to develop our first inhibitor but it was Sotorasib which was FDA approved in 2021 we have adigrasiv that's already submitted to the fda as a new drug designation and in ASCO 2022 there were multiple updates about this promising treatment as well and there's over a dozen other K-RAS 212C inhibitors under development additionally i go into some of the non-uh G12C targeting medicines and i think they highlight the ingenuity and also progress that we've made in medicinal chemistry and drug development since some of these approaches include those that are molecules that induce new protein protein interactions or those that are clever small molecule inhibitors that are targeting the non-G12C isoform so overall i end the talk by saying that due to these many molecules that are being developed in the clinic and great excitement in this field since our breakthrough in 2013 of developing a new krs G12C inhibitor that we should keep up the momentum by testing all of our patients who have advanced non-small cell lung cancer for K-RAS alterations and it shouldn't just be the medical oncologists I think proceduralists pathologists and others should be aware of this as well so please check out my presentation at ASCO 2022 taking on Goliath to find out more about K-RAS lung cancers thank you

Article: Transcript: Targeting K-RAS in Lung Cancer is a Goliath Task (But We Have Some Answers) - Jia Luo, MD @Jia_L...

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