Abstract
Tumours with sensitizing mutations in the EGFR gene constitute a distinct molecular subgroup of non-small-cell lung cancers (nsclcs) that benefit from precision medicine. First- and second-generation epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as upfront therapy for EGFR-mutated advanced nsclc and, compared with chemotherapy, have resulted in superior progression-free survival, improved tumour response rates, and improved quality of life. However, resistance inevitably develops, and the third-generation tki osimertinib has been approved to target the gatekeeper EGFR mutation T790M, which is responsible for resistance in 60% of cases. Multiple drivers of tki resistance have now been identified, and many new drugs are in development. With respect to this rapidly evolving field, our review highlights the current status of treatment options for patients with EGFR-mutated advanced nsclc, focusing especially on identified causes of resistance, challenges, and clinical trials aiming to improve outcomes in this patient population.
Highlights
Breast cancer has overtaken lung cancer as the most commonly diagnosed cancer globally in 2020 [1]
Non-negative matrix factorization (NMF) clustering was used to classify them into two groups named HAM1 and HAM2 (Figure 2)
Various patterns of expression were noticed for the eight genes which suggest that the histone acetylation modulators (HAMs) groups could be very different from the PAM50 intrinsic subtypes
Summary
Breast cancer has overtaken lung cancer as the most commonly diagnosed cancer globally in 2020 [1]. Breast cancer is widely accepted as a highly heterogeneous disease. The current approach to classifying breast cancer into clinical subtypes is based on the immunohistochemistry (IHC) results of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki67. This IHC based clinical subtyping system is not ideal, and gene expression profiling (intrinsic subtyping) reveals a deeper appreciation for the disease heterogeneity [2]. In 2000, Perou et al developed the PAM50 intrinsic subtypes of breast cancer based on a set of 50 genes [3]. Various other tests based on gene expression quantification have been developed to provide molecular stratification of breast cancer [4]
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