Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10–20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high degree of heterogeneity in its histology, a genomic landscape, and response to therapies that has been traditionally difficult to reproduce in preclinical models. However, the advent of three-dimensional culture technologies has opened new perspectives to recapitulate in vitro individualized tumor features and to anticipate treatment efficacy. The generation of lung cancer organoids (LCOs) has encountered greater challenges as compared to organoids derived from other tumors. In the last two years, many efforts have been dedicated to optimizing LCO-based platforms, resulting in improved rates of LCO production, purity, culture timing, and long-term expansion. However, due to the complexity of lung cancer, further advances are required in order to meet clinical needs. Here, we discuss the evolution of LCO technology and the use of LCOs in basic and translational lung cancer research. Although the field of LCOs is still in its infancy, its prospective development will likely lead to new strategies for drug testing and biomarker identification, thus allowing a more personalized therapeutic approach for lung cancer patients.
Metastasis is the primary cause of death in patients with colorectal cancer (CRC), urging the need for preclinical models that recapitulate the metastatic process at the individual patient level. We used an orthotopic patient-derived xenograft (PDX) obtained through the direct implantation of freshly dissociated CRC cells in the colon of immunocompromised mice to model the metastatic process. Ortho-PDX engraftment was associated to a specific set of molecular features of the parental tumor, such as epithelial-to-mesenchymal transition (EMT), TGF-β pathway activation, increased expression of stemness-associated factors and higher numbers of circulating tumor cells (CTCs) clusters expressing the metastatic marker CD44v6. A parallel analysis of orthotopic/metastatic xenografts and organoids showed that tumor cells underwent mesenchymal-to-epithelial transition at the metastatic site and that metastasis-derived organoids had increased chemotherapy resistance. These observations support the usefulness of ortho-PDX as a preclinical model to study metastasis-related features and provide preliminary evidence that EMT/stemness properties of primary colorectal tumors may be crucial for orthotopic tumor engraftment.
Inguinal hernia repair is one of the most common surgical procedures in the world. Currently, recurrence rates have reduced to less than 5% after mesh repair, but chronic groin pain (CGP) remains a major concern in open hernia surgery. The aim of the study was to detect neuropathic pain associated with iatrogenic nerve damage using the dermatome mapping test (DMT) and to evaluate the preventability of CPG.The study was designed and conducted as a prospective longitudinal observation study in postoperative open hernioplasty patients. The study included 71 adult patients with a primary inguinal hernia, who underwent a standard open surgical procedure for hernia repair using a polypropylene mesh (Lichtenstein's technique). The dermatome mapping classification was performed in each patient, and the test results were recorded. Seven (9.9%) patients with surgery-related pain lasting for three months or longer after surgery were considered to have CGP, and pain was related to iatrogenic nerve damage in two of these cases. Based on the results, we consider that the anatomical location of the nerves can be easily determined using DMT, and CGP can be prevented.
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