A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists

Garajová, Ingrid; Peroni, Marianna; Gelsomino, Fabio; Leonardi, Francesco

doi:10.3390/curroncol30110694

Cited by 9 publications

(2 citation statements)

References 110 publications

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“…Besides surgical resection, for which a small portion of patients are eligible, chemotherapy is the only available treatment. Currently, the combination-regimens FOLFIRINOX or gemcitabine plus nab-paclitaxel are being employed to treat patients with inoperable PDAC [3]. However, in the majority of the patients rapid chemoresistance occurs, with the underlying biological mechanisms remaining largely elusive.…”

Section: Introductionmentioning

confidence: 99%

Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel

Gregori,

Bergonzini,

Capula

et al. 2024

Preprint

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Background: Pancreatic ductal adenocarcinoma (PDAC) acquired resistance to chemotherapy poses a major limitation to patient survival. Despite understanding of some biological mechanisms of chemoresistance, much of those mechanisms remain to be uncovered. Mechanobiology, which studies physical properties of cells, holds promise as a potential target for addressing challenges of chemoresistance in PDAC. Therefore, we here in an initial step, assessed the altered mechanobiology of PDAC cells with acquired chemoresistance to gemcitabine and paclitaxel. Methods: Five PDAC cell lines and six stably-resistant subclones were assessed for force generation on elastic micropillar arrays. Those measurements of mechanical phenotype were complemented by single-cell motility and invasion in collagen matrix were investigated using 2D models and 3D extracellular matrix-mimetic, respectively. Further the nuclear translocation of Yes-associted protein (YAP), as a measure of active mechanical status, was compared, and biomarkers of the epithelial-to-mesenchymal transition (EMT) were evaluated using RT-PCR. Results: PDAC cells with acquired chemoresistance exert higher traction forces than their parental/wild-type (WT) cells. In 2D, single-cell motility was altered for all chemoresistant cells, with a cell-type specific pattern. In 3D, spheroids of chemoresistant PDAC cells were able to invade the matrix, and remodel collagen more than their WT clones. However, YAP nuclear translocation and EMT were not significantly altered in relation to changes in other physical parameters. Conclusion: This is the first study to investigate and report on the altered mechanobiological features for PDAC cells that have acquired chemoresistance. A better understanding of mechanical features could help in identifying future targets to overcome chemoresistance in PDAC.

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Section: Introductionmentioning

confidence: 99%

Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel

Gregori,

Bergonzini,

Capula

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…The cost of pancreatic cancer treatment is extremely expensive and ineffective, which puts a heavy nancial burden on patients. Currently, the main treatments for pancreatic cancer in clinical practice including surgery (pancreatoduodenectomy), chemotherapy, radiation therapy, and targeted drug therapy [5][6].…”

Section: Introductionmentioning

confidence: 99%

Race/Ethnicity, Age, Gender Disparities among Pancreatic Cancer Patients: A Study based on SEER Database

qing,

Xu,

Huang

et al. 2024

Preprint

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Background: Pancreatic cancer is one of the most common malignancies of the digestive system. This study aimed to explore the disparities in incidence and survival across various races, ages, and genders. Methods: Data from the SEER 17 Registries Database, encompassing primary malignant pancreatic cancer cases diagnosed from 2016 to 2020, were analyzed. This study compared patients under the age of 50 with the whole population. Chi-square test evaluated the statistical significance of disparities in race/ethnicity, age, gender, cancer stages, and survival times.. Kaplan-Meier survival curve assessed survival differences by race/ethnicity, age, and gender, and using Annual Average Percentage Change to assess incidence trends. Results:The study included 33,151 patients, comprising 21,309 (64.2%) Whites, 3,817 (11.6%) Blacks, 207 (0.6%) American Indian/Alaska Natives, 2,984 (9.0%) Asians or Pacific Islanders, and 4,780 (14.4%) Hispanics. The findings revealed significant disparities in incidence and mortality rates among different racial and ethnic groups, with Blacks demonstrated notably higher rates. Most diagnosed with pancreatic cancer were elderly,, mainly concentrated in 50-69 years old, patients under 50 had higher survival rate than other age groups. The number of male patients was higher than that of female, with 52.5% of males and 47.4% of females. However, gender-based survival differences in patients under 50 were insignificant. Conclusion: The study revealed significant differences in incidence and survival rate among patients. These findings are important to further understand the factors that affect pancreatic cancer, and enhance the monitoring of people at high risk.

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Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer

Urabe,

Ikezawa,

Seiki

et al. 2024

Sci Rep

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Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP’s therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

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A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists

Cited by 9 publications

References 110 publications

Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel

Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel

Race/Ethnicity, Age, Gender Disparities among Pancreatic Cancer Patients: A Study based on SEER Database

Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer

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