Browsing by Subject "Therapy resistance"

Now showing 1 - 3 of 3
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    Assessment of estrogen receptor low positive status in breast cancer: Implications for pathologists and oncologists
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Fusco, Nicola; Ragazzi, Moira; Sajjadi, Elham; Venetis, Konstantinos; Piciotti, Roberto; Morganti, Stefania; Santandrea, Giacomo; Fanelli, Giuseppe Nicolò; Despini, Luca; Invernizzi, Marco; Cerbelli, Bruna; Scatena, Cristian; Criscitiello, Carmen
    Estrogen receptor (ER) status assessment by immunohistochemistry (IHC) is the gold standard test for the identification of patients with breast cancer who may benefit from endocrine therapy (ET). Whilst most ER+ breast cancers have a high IHC score, about 3% of cases display a low positivity, with 1% to 10% of cells being weakly stained. These tumors are generally classified within the luminal-like category; however, their risk profile seems to be more similar to that of ERnegative breast cancers. The decision on ET for patients with a diagnosis of ER-low breast cancer should be carefully considered in light of the risks and possible benefits of the treatment. Potential pitfalls hinder pathologists and oncologists from establishing an appropriate threshold for "low positivity". Furthermore, several pre-analytical and analytical variables might trouble the pathological identification of these clinically challenging cases. In this review, we sought to discuss the adversities that can be accounted for the pathological identification of ER-low breast cancers in real-world clinical practice, and to provide practical suggestions for the perfect ER testing in light of the most updated recommendations and guidelines.
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    Comparable expression of stem markers and damage-responsive proteins in untreated and chemoradiation-treated rectal cancer
    (2026) Sachi Sekine; Hirotoshi Kawata; Tomoko Kamiakito; Takeo Nakaya; Yasuyuki Miyakura; Koichi Suzuki; Toshiki Rikiyama; Akira Tanaka1; Kentaro Tsuji; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
    Purpose. Cancer stem cells (CSCs) are suggested to contribute to therapy resistance in rectal cancer. However, histopathological analysis of CSCs is still lacking in rectal cancer. Methods. The expression of leucine-rich, repeat containing G protein-coupled receptor 5 (LGR5), proto oncogene, polycomb ring finger 1 (BMI1), yes associated transcriptional regulator (YAP) and its paralog TAZ (hereafter, YAP/TAZ), and nuclear β catenin was compared in untreated and chemoradiation treated (CRT) rectal cancer by in situ hybridization and immunostaining. Niche factors were also compared in human rectal cancer specimens and the embryonic intestine. Results. The mean ratios were 15% and 14% for LGR5, 30% and 33% for BMI1, 2.7% and 7.6% for YAP/TAZ, and 38% and 32% for nuclear β-catenin in untreated and CRT rectal cancer, respectively, showing no significant differences for these stem markers following CRT. The stromal expression ratios of YAP/TAZ were 9.7% and 23% in untreated and CRT rectal cancer, which indicated significant upregulation and confirmation of the damage response in the stroma of CRT tumors. In addition, cancer cells co-expressing LGR5 and CDKN1B are also comparable in untreated and CRT rectal cancer. For niche factors, we found that WNT2B and GREM1 were uniformly expressed in rectal cancer with a pattern similar to that of the early embryonic intestine. Conclusion. The expression of LGR5, BMI1, CDKN1B, and YAP/TAZ was comparable in untreated and CRT rectal cancer. The uniform expression of mesenchymal niche factors might prevent the zonation of the stem cell niche in rectal cancer
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    Metastatic dormancy: a complex network between cancer stem cells and their microenvironment
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Bleau, Anne-Marie; Agliano, Alice; Larzabal, Leyre; Lopez de Aberasturi, Arrate; Calvo, Alfonso
    Metastasis represents the major threat of cancer progression and generally emerges years after the detection of the primary tumor. An important ratelimiting step resides in cellular dormancy, where a disseminated tumor cell remains in a quiescent state at a remote organ. Herein we review the molecular mechanisms leading to tumor dormancy, mainly in regards to cellular quiescence and the tumor microenvironment. Based on the current published literature, we provide evidence that links the cancer stem cell (CSC) theory with dormancy and metastasis. Once a disseminated tumor cell reaches a target tissue, a tight regulation imposed by the foreign microenvironment will dictate the fate of these cells, which implies a balance in the secretion of soluble factors, modulation of the extracellular matrix and the angiogenic switch. We investigate thoroughly whether the CSC theory could also apply to metastasis initiation. In fact, the resistance of CSCs to therapy, leading to the minimal residual disease and cellular quiescence phenotypes, predisposes for the development of metastases. Finally, we describe the new technologies available for the identification of circulating tumor cells (CTCs), as well as their clinical relevance in dormancy of metastatic cancer patients.