Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown Read more in PDF.
Lung cancer has gained worldwide a top place in the incidence and mortality related to malignancy. Out of the two different types of pulmonary neoplasms, the histological subtypes included in non-small cell category have received a particular interest because of the various therapeutic targets identified. In the recent years, due to its promising results, the development of immunotherapy is considered a major discovery and has become one of the main therapeutic options along with chemotherapy, radiotherapy and surgery. In order to determine the selection of patients who can obtain beneficial approach from immune checkpoint inhibitors treatment, programmed death-ligand 1 (PD-L1) expression evidenced by immunohistochemistry (IHC) testing has been implemented as a complementary or as a mandatory diagnostic tool in patients with advanced non-small cell lung cancer (NSCLC). The developing studies in this field were concentrated upon the importance of the expression of PD-L1 as a predictive biomarker for treatment response and patients selection validated into clinical daily practice. The aim of this review is to enlighten the factors which influence PD-L1 expression and the utility as biomarker in immunotherapy. RezumatCancerul bronhopulmonar a câștigat un loc fruntaș în topul incidenței și al mortalității de cauză malignă la nivel global. În cadrul cele două tipuri diferite de neoplasm pulmonar, subtipurile histologice care aparțin categoriei "fără celule mici" au dobândit un interes particular datorită numeroaselor ținte terapeutice identificate. În ultimii ani, conform rezultatelor promițătoare oferite, imunoterapia este considerată o descoperire importantă și a devenit una dintre principalele opțiuni terapeutice alături de chimioterapie, radioterapie și chirurgie. Cu scopul de a selecta pacienții care vor beneficia de tratament cu inhibitori ai punctelor de control imun, expresia ligandului morții celulare programate 1 (PD-L1) evidențiată prin imunohistochimie (IHC) a fost folosită ca metodă de diagnostic complementară sau condiționată la pacienții cu neoplasm bronhopulmonar fără celule mici. Studiile desfășurate în acest domeniu s-au concentrat asupra valorii expresiei PD-L1 ca și biomarker predictiv al răspunsului la tratament și al selectării pacienților, aplicabil în practica medicală zilnică. Scopul acestui review este de a evidenția factorii care influențează expresia PD-L1 și utilitatea sa ca biomarker în tratamentul cu inhibitori ai punctelor de control imun.
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