Synthetic 3D multicellular systems derived from patient tumors, or tumoroids, have been developed to complete the cancer research arsenal and overcome the limits of current preclinical models. They aim to represent the molecular and structural heterogeneity of the tumor micro-environment, and its complex network of interactions, with greater accuracy. They are more predictive of clinical outcomes, of adverse events, and of resistance mechanisms. Thus, they increase the success rate of drug development, and help clinicians in their decision-making process. Lung cancer remains amongst the deadliest of diseases, and still requires intensive research. In this review, we analyze the merits and drawbacks of the current preclinical models used in lung cancer research, and the position of tumoroids. The introduction of immune cells and healthy regulatory cells in autologous tumoroid models has enabled their application to most recent therapeutic concepts. The possibility of deriving tumoroids from primary tumors within reasonable time has opened a direct approach to patient-specific features, supporting their future role in precision medicine.
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http://dx.doi.org/10.3390/biomedicines10071677 | DOI Listing |
Toxicol Sci
January 2025
Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDFJ Psychopathol Clin Sci
January 2025
Department of Human Development and Family Studies, Pennsylvania State University.
Ecological momentary assessment is increasingly leveraged to better understand affective processes underlying substance use disorder treatment and recovery. Research in this area has yielded novel insights into the roles of mean levels of positive affect (PA) and negative affect (NA) in precipitating drug craving and substance use in daily life. Little of the extant substance use disorder treatment research, however, considers dynamic patterns of PA and NA, separately or in relation to one another, or how such patterns may differ from those observed among nonclinical samples.
View Article and Find Full Text PDFDermatitis
January 2025
From the Department of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Eczema and dermatitis are common inflammatory skin conditions with significant morbidity. Identifying drug-targetable genes can facilitate the development of effective treatments. This study analyzed data obtained by meta-analysis of 2 genome-wide association studies on eczema/dermatitis (57,311 cases and 896,779 controls, European ancestry).
View Article and Find Full Text PDFDermatol Ther (Heidelb)
January 2025
Dermatological Centre in Milan, Milan, Italy.
Acne and acne sequelae can have an important impact on patients' quality of life, affecting interpersonal relationships and social functioning. Acne-induced scars (AIS) and acne-induced macular hyperpigmentation (AIH), in particular, are a major concern for patients with acne, as their management is challenging and often unsatisfactory. Retinoids are considered the mainstay of acne treatment because of their action on multiple pathogenetic factors, and there is increasing evidence that they can also improve AIS and AIH.
View Article and Find Full Text PDFCurr Treat Options Oncol
January 2025
Breast Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Breast cancer metastasizing to the central nervous system (CNS) encompasses two distinct entities: brain metastases involving the cerebral parenchyma and infiltration of the leptomeningeal space, i.e., leptomeningeal disease.
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