Small Cell Transformation and T790M Mutation as Coresistance Mechanisms for First-line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy Failure

Molecular biomarker testing of advanced‐stage NSCLC is now considered standard of care and part of the diagnostic algorithm to identify subsets of patients for molecular‐targeted treatment. Tumour tissue biopsy is essential for an accurate initial diagnosis, determination of the histological subtype and for molecular testing. With the increasing use of small biopsies and cytological specimens for diagnosis and the need to identify an increasing number of predictive biomarkers, proper management of the limited amount of sampling materials available is important. Many patients with advanced NSCLC do not have enough tissue for molecular testing and/or do not have a biopsy‐amenable lesion and/or do not want to go through a repeat biopsy given the potential risks. Molecular testing can be difficult or impossible if the sparse material from very small biopsy specimens has already been exhausted for routine diagnostic purposes. A limited diagnostic workup is recommended to preserve sufficient tissue for biomarker testing. In addition, tumour biopsies are limited by tumour heterogeneity, particularly in the setting of disease resistance, and thus may yield false‐negative results. Hence, there have been considerable efforts to determine if liquid biopsy in which molecular alterations can be non‐invasively identified in plasma cell‐free ctDNA, a potential surrogate for the entire tumour genome, can overcome the issues with tissue biopsies and replace the need for the latter.

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How to Keep Up With Molecular Testing and Targeted Therapies in Lung Cancer

Malhotra,

Kim

2024

JCO Oncol Pract

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Until the early 2000s, advanced or metastatic non–small cell lung cancer (NSCLC) was treated as a single disease with all histologic subtypes treated alike with standard chemotherapy agents. Over the past two decades, the treatment paradigms for advanced NSCLC have changed dramatically with the discovery of multiple targeted therapies that are now approved for the treatment of NSCLC tumors with specific oncogene drivers or molecular alterations. Molecular testing has become integrated and critical for the clinical management of advanced NSCLC. The discovery and success of these targeted therapies have reshaped the classification of NSCLC on the basis of molecular classification and enabled a personalized approach in thoracic oncology. In this review, we discuss recent developments in the molecular profiling of NSCLC, and approved and emerging targeted therapies for the treatment of NSCLC.

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Small Cell Transformation and T790M Mutation as Coresistance Mechanisms for First-line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy Failure

Cited by 3 publications

References 5 publications

Afatinib/gefitinib

Afatinib/gefitinib

Is tissue still the issue in detecting molecular alterations in lung cancer?

How to Keep Up With Molecular Testing and Targeted Therapies in Lung Cancer

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