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1.
Front Immunol ; 15: 1366260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655260

RESUMO

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Imunoterapia , Neoplasias Pulmonares , Terapia de Alvo Molecular , Microambiente Tumoral , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/imunologia , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Animais , Biomarcadores Tumorais
2.
Front Oncol ; 13: 1296456, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098505

RESUMO

Mitochondrial heat shock protein 90 (mtHsp90), including Tumor necrosis factor receptor-associated protein 1 (TRAP1) and Hsp90 translocated from cytoplasm, modulating cellular metabolism and signaling pathways by altering the conformation, activity, and stability of numerous client proteins, and is highly expressed in tumors. mtHsp90 inhibition results in the destabilization and eventual degradation of its client proteins, leading to interference with various tumor-related pathways and efficient control of cancer cell development. Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.

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