Molecular Heterogeneity in Non-Small Cell Lung Cancer

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In this segment, Alan B. Sandler, MD, Corey J. Langer, MD, Anne S. Tsao, MD, Mark A. Socinski, MD, and David Gandara, MD, discuss the heterogeneity of molecular characteristics in non-small cell lung cancer.

Sandler begins the conversation by noting that differences within tumors exist and that a biopsy only takes a small sample of what could be a very heterogenous tumor. For the most part, Langer agrees with Sandler but emphasizes the idea that a disease does not lose mutations and is not so much heterogenous as it is evolving.

Tsao says that she routinely biopsies a growing metastatic lesion in patients with an EGFR or ALK mutation.

With the emergence of other clones, resistant tumors may be quite heterogenous, Socinski says, and rebiopsying may be the only way to gauge what's going on. The question with many mutations is whether or not they are undetected from the beginning or if they emerged over time.

Gandara recaps the conversation by mentioning that there are new and sensitive techniques, such as scorpion technology, to detect mutations. Gandara says that T790M is present in up to 1/3 of patients with activating mutations in their cancer. He stresses the need for more sensitive techniques to determine whether the second driver was there in the beginning and developed under the influence of therapy or if it was there as an unidentifiable clone.