Comparison of molecular subtype composition between independent sets of primary and brain metastatic small cell lung carcinoma and matched samples.

Introduction: Recent advances in the subclassification of small cell lung carcinomas (SCLCs) may help to overcome the unmet need for targeted therapies and improve survival. However, limited information is available on how the expression of the subtype markers changes during tumour progression. Our study aimed to compare the expression of these markers in primary and brain metastatic SCLCs.

Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression.

Small cell lung carcinoma (SCLC) is a highly malignant cancer with early metastatic dissemination and poor clinical outcomes. Mutations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, including the frequently occurring rapamycin-insensitive protein (RICTOR) amplification, have been described in these tumours. Moreover, the associated mTOR hyperactivity could be exploited for personalised treatment.

mTOR hyperactivity and amplification as targets for personalized treatments in malignancies.

The increasing knowledge of molecular alterations in malignancies, including mutations and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway, highlights the importance of mTOR hyperactivity as a validated target in common and rare malignancies. This review summarises recent findings on the characterization and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity. We have recently identified new tumor types with (rapamycin-insensitive companion of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets for developing targeted therapies in lung cancer and other newly described malignancies.

Rictor-A Mediator of Progression and Metastasis in Lung Cancer.

Lung carcinoma is one of the most common cancer types for both men and women. Despite recent breakthroughs in targeted therapy and immunotherapy, it is characterized by a high metastatic rate, which can significantly affect quality of life and prognosis. Rictor (encoded by the gene) is known as a scaffold protein for the multiprotein complex mTORC2.

[Effects of 3D tissue structure on drug sensitivity - 3D bioprinted tissue mimetic structures in cancer research].

The issues surrounding the cost effectiveness of drug development and the ethical concerns associated with animal testing, emphasise the necessity for innovative in vitro models that allow enhanced pre-selection. Therefore, we aim to create 3D bioprinted tissue mimetic structures (TMS) utilizing various human cancer cell lines. We have generated TMSs from human tumour cell lines (breast, kidney, glioma), with detailed characterisation of the ZR75.

[he importance of mTOR hyperactivity and RICTOR amplification, and the associated targeted therapy possibilities in malignant tumours].

Failures of anti-tumour therapies and drug resistance initiate difficulties in cancer treatments often caused by alterations in signalling network activity, including PI3K/Akt/mTOR hyperactivity due to oncogenic mutations. In this review, we summarise the relevance of mTOR (mechanistic target of rapamycin) dysregulation identified decades ago, which is now known to be characteristic of many tumours. In this context, we present differences in activity, function and testability of mTOR kinase complexes (mTORC1 and mTORC2) differing in structure, regulatory mechanisms and inhibitor sensitivity.