What Patients With Lung Cancer Need to Know About EGFR PACC Mutations

Lung cancer research has recognized the role of EGFR mutations in driving the disease for about 20 years, with most patients presenting with common "classical" mutations, specifically the exon 19 deletion or the L858R mutation, as one expert explained in an interview with CURE. As diagnostic techniques have evolved, particularly with the widespread use of next-generation sequencing, a growing number of uncommon EGFR mutations are being discovered.

Dr. Xiuning Le, an associate professor in the Department of Thoracic/Head and Neck Medical Oncology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center in Houston, sat down for an interview with CURE during the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer.

In the interview, Le highlighted a specific type of uncommon mutation known as PACC, which causes a significant alteration in the protein's structure, which explains why traditional EGFR tyrosine kinase inhibitor (TKI) treatments, which are highly effective for classical mutations, do not work for patients with PACC mutations.This therapeutic mismatch creates a critical "unmet need" in oncology, Le said.

Transcript:

What are EGFR PACC mutations? Why is it important to study new treatments for this group of lung cancers?

As a field, we've known EGFR mutations can drive lung cancer for about 20 years. Most of the patients have one of two types of mutation. We call them classical mutation, either a deletion in part of the exon 19, or L858R mutation. Over time, we have more approaches or we have more testing in the next-generation sequencing nowadays, so we detected more uncommon EGFR mutations. PACC stands for compress of the alpha c-helix compression domain. That means when the uncommon EGFR mutation happens, this alteration of the structure is different than the classical mutation. Because of that, the treatment for classical mutation, other EGFR TKI, doesn't work well for this patient population. That creates the unmet need. Just imagine if the tumor has a PACC mutation and received the other EGFR TKI, patients don't do well, then that's a problem. We're looking forward to seeing newer EGFR TKI fitting in particular the PACC mutation. That's where we talk about precision oncology.

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.