Meta-analysis of the prognostic impact of TP53 co-mutations in EGFR-mutant advanced non-small-cell lung cancer treated with tyrosine kinase inhibitors

Purpose: To assess the prognostic impact of TP53 mutations in EGFR-mutant advanced NSCLC patients treated with TKIs. Methods: Studies exploring the clinical outcomes of EGFR mutant/TP53 wild-type versus EGFR/TP53 co-mutant patients treated with TKIs were selected. Data were cumulated by adopting a fixed and random-effect model. Results: Overall, 29 trials were eligible. The PFS analysis showed that TP53 co-mutant group has shorter PFS versus EGFR mutant/TP53 wild-type group (HR = 1.67, 95% CI 1.51-1.83, heterogeneity I2 =20%, p = 0.18). Patients affected by EGFR/TP53 co-mutant NSCLC have a higher chance of shorter OS versus EGFR mutant/TP53 wild type (HR= 1.89, 95% CI 1.67-2.14, heterogeneity I2 = 21%; p = 0.19). The subgroup analysis showed no significant difference between first-second versus third-generation TKIs in both PFS and OS (p = 0.31, p = 0.08). Conclusions: TP53 mutations represent a clinically relevant mechanism of resistance to EGFR-TKIs, regardless of their generation. A personalized therapeutical approach should be explored in dedicated clinical trials

Extracellular Vesicles and Artificial Intelligence: Unique Weapons against Breast Cancer

Breast cancer (BC) caused 685,000 deaths globally in 2020, earning the title of the most common type of tumor among females. With a multifactorial genesis, BC is influenced by several factors such as age, genetic and epigenetic predisposition, and an individual’s exposome, and its classification is based on morphological/histological, invasiveness, and molecular futures. Extracellular vesicles (EVs) are cell-derived lipid-bilayer-delimited nanoparticles, which are distinguishable by size, genesis, and the markers expressed in exosomes (40 to 150 nm), microvesicles (40 to 10,000 nm), and apoptotic bodies (100–5000 nm). Produced in physiological and pathological cellular contexts, EVs are shuttles of biological material and are implicated in cell-to-cell communications, thus attracting significant interest in diagnostic and drug delivery research. We report and discuss the latest evidence regarding the important role of EVs in BC, deepening their implication in tumorigenesis and metastatic mechanisms. On the other hand, the use of BC-derived EVs as prognostic biomarkers and therapeutic approaches is undergoing investigation. Hence, EVs have become new weapons in precision medicine; however, only with the support of advanced algorithms such as artificial intelligence (AI) can we develop a wide range of information. Looking ahead, it is possible to see the application of AI in the prognosis and diagnosis of different pathologies