https://www.jto.org/article/S1556-0864(16)30457-9/pdf

S768I Mutation in EGFR in Patients with Lung Cancer

Persistent infection of Mycoplasma hyorhinis (M. hyorhinis) was associated with gastric cancer cell migration and invasion, but the mechanisms were not well understood. Herein, we found that M. hyorhinis activated phosphoinositide 3-kinase (PI3K)-AKT signaling axis in gastric cancer cell lines. Epidermal growth factor receptor (EGFR) was upstream of PI3K-AKT signaling in the context of M. hyorhinis infection, because phosphorylation of AKT Serine 473 was almost completely attenuated by the EGFR inhibitor AG1478 or by EGFR knockdown. Phosphorylation of AKT S473 induced by M. hyorhinis infection was also abolished by PI3K inhibitor wortmannin. Furthermore, we found that p37, a membrane protein of M. hyorhinis, could also promote M. hyorhinis-induced PI3K-AKT signaling activation and cell migration. In addition, pre-treatment with AG1478 or wortmannin significantly inhibited cell migration induced by M. hyorhinis infection or p37 treatment. In conclusion, EGFR-PI3K-AKT signaling plays an important role in M. hyorhinis-promoted cell migration in gastric cancer cells, thus providing a clue to the pathogenesis of M. hyorhinis in gastric cancer.

/pdf/activation-of-egfr-pi3k-akt-signaling-is-required-for-29tc335k3z.pdf

Activation of EGFR-PI3K-AKT signaling is required for Mycoplasma hyorhinis-promoted gastric cancer cell migration

Recently, the development of the third-generation epidermal growth factor receptor-small molecule inhibitor (EGFR-TKI) rociletinib had failed. In this review, the wide-ranging aspects of the evolution of EGFR-TKIs were collected, with a special focus on rociletinib. The influence of different oncogenic mutations on EGFR activity was also discussed. Resistance to the first (erlotinib, gefitinib)- and second (afatinib)-generation EGFR-TKIs provided the rationale behind the development of the third-generation inhibitors (rociletinib, osimertinib). On the basis of these data, a comparison of their efficacy on the different mutated EGFRs and the respective resistance mechanisms is further reported. Moreover, the evolution and results of the clinical trials of rociletinib (TIGER trials) are compared with the trials on osimertinib, another third-generation EGFR-TKI that now has been granted US Food and Drug Administration approval. The reasons behind the arrest in the further development of rociletinib are put in the perspective of future drug development.

/pdf/new-developments-in-the-management-of-non-small-cell-lung-4rpcoxcp6m.pdf

New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?

Double Trouble: A Case Series on Concomitant Genetic Aberrations in NSCLC.

Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer Whose Tumors Harbor Uncommon Epidermal Growth Factor Receptors Mutations

Tony Mok

Papers

Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer Whose Tumors Harbor Uncommon Epidermal Growth Factor Receptors Mutations

D2-07: Mechanisms of activating PI3K signaling in lung cancers that become resistant EGFR tyrosine kinase inhibitors