Treatment landscape of metastatic pancreatic cancer

Dosso, Sara De; Siebenhüner, Alexander; Winder, Thomas; Meisel, Alexander; Fritsch, Ralph; Astaras, Christoforos; Szturz, Petr; Borner, Markus

doi:10.1016/j.ctrv.2021.102180

Cited by 126 publications

(89 citation statements)

References 70 publications

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“…Late diagnosis, due to delayed manifestation of symptoms and generally very poor long-term response to systemic chemotherapy have complicated the treatment and resulted in worse outcomes for patients, hence these are now subject to state-of-the-art studies in the precision medicine field ( 5 ). Hence, the search for new diagnostic, prognostic and predictive biomarkers which will facilitate treatment at less advanced stages when outcomes are more favorable is necessary ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Gene expression of cytokinesis regulators PRC1, KIF14 and CIT has no prognostic role in colorectal and pancreatic cancer

et al. 2021

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Colorectal cancer is one of the most common cancers and pancreatic cancer is among the most fatal and difficult to treat. New prognostic biomarkers are urgently needed to improve the treatment of colorectal and pancreatic cancer. Protein regulating cytokinesis 1 ( PRC1 ), kinesin family member 14 ( KIF14 ) and citron Rho-interacting serine/threonine kinase ( CIT ) serve important roles in cytokinesis, are strongly associated with cancer progression and have prognostic potential. The present study aimed to investigate the prognostic relevance of the PRC1, KIF14 and CIT genes in colorectal and pancreatic cancer. PRC1, KIF14 and CIT transcript expression was assessed by reverse transcription-quantitative PCR in tumors and paired distant unaffected mucosa from 67 patients with colorectal cancer and tumors and paired non-neoplastic control tissues from 48 patients with pancreatic cancer. The extent of transcript dysregulation between tumor and control tissues and between groups of patients divided by main clinical characteristics, namely patients' age and sex, disease stage, localization and grade, was determined. Finally, the associations of transcript levels in tumors with disease-free interval and overall survival time were evaluated. PRC1, KIF14 and CIT transcripts were upregulated in tumors compared with control tissues. PRC1, KIF14 and CIT levels strongly correlated to each other in both colorectal and pancreatic tumor and control tissues after correction for multiple testing. However, no significant associations were found among the transcript levels of PRC1, KIF14 and CIT and disease-free interval or overall survival time. In summary, the present study demonstrated mutual correlation of PRC1, KIF14 and CIT cytokinesis regulators with no clear prognostic value in pancreatic and colorectal cancers. Hence, according to the results of the present study, transcript levels of these genes cannot be clinically exploited as prognostic biomarkers in colorectal or pancreatic cancer patients.

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Section: Introductionmentioning

confidence: 99%

Gene expression of cytokinesis regulators PRC1, KIF14 and CIT has no prognostic role in colorectal and pancreatic cancer

et al. 2021

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“…22 In Switzerland, the most frequently utilized first-line drug therapy for locally advanced unresectable or metastatic PDAC is gemcitabine plus nab-paclitaxel. 23 The approval of this combination was based on the results from the phase III MPACT trial, which showed that gemcitabine plus nab-paclitaxel were associated with significantly improved long-term survival outcomes compared with gemcitabine alone. 24,25 In the primary analysis of the trial, treatment with the doublet led to a significantly improved median OS versus gemcitabine alone (8.5 months vs 6.7 months, HR: 0.72 [95% CI: 0.62−0.83]; p<0.001).…”

Section: First-line Palliative Settingmentioning

confidence: 99%

“…In Switzerland, a group of clinicians has built a consensus on the treatment strategy of metastatic PDAC in the first-line setting. 23 The most used therapy is gemcitabine plus nabpaclitaxel, while in young (age below 65 years) and fit (ECOG PS of 0−1) patients with normal bilirubin levels, treatment with FOLFIRINOX can also be considered (Figure 1).…”

Section: First-line Palliative Settingmentioning

confidence: 99%

“…29 In order to optimize the continuum of care for patients with PDAC, first-line treatment choice should be based on the availability and overlap with potential second-line options. 23 For example, there is no clinically validated secondline option after progression on frontline FOLFIRINOX, while gemcitabine plus nab-paclitaxel allow for second-line treatment with nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV), the only secondline therapy for metastatic pancreatic cancer that has shown a survival advantage in a phase III study, after progression to a gemcitabine-based regimen. 30…”

Section: First-line Palliative Settingmentioning

confidence: 99%

“…In Swiss clinics, genetic testing of UGT1A1 polymorphisms prior to nal-IRI treatment is not routinely done. 23 Although it is recommended, no clear guidelines regarding its applicability are available and as an option, it is possible to start at a lower dose level as a precaution, without affecting the overall efficacy.…”

Section: Second-line Palliative Settingmentioning

confidence: 99%

See 2 more Smart Citations

Metastatic Pancreatic Cancer: Current Treatment Options for Swiss Patients

Dosso¹,

Siebenhüner²,

Winder³

et al. 2021

healthbook TIMES Onco Hema

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Despite oncological advances over the past years, survival outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. For most PDAC patients, the disease is often asymptomatic at early phases and is therefore typically diagnosed at the advanced or metastatic stage. As a result, up to 85% of the cases are unresectable, and systemic chemotherapy is the predominant treatment modality for this patient population. While the current therapeutic strategies for the local disease include surgical resection and adjuvant chemotherapy, FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens are the frontline standard of care in the unresectable locally advanced and metastatic settings. In Switzerland, nanoliposomal irinotecan (nal-IRI) is currently the only regimen approved in the second line following progression on gemcitabine plus nab-paclitaxel, based on the results from the phase III NAPOLI-1 trial. Recently, olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and larotrectinib, a first-in-class tropomyosin receptor kinases (TRK) inhibitor, were added to the treatment armamentarium of patients with a molecularly-defined subset of metastatic adenocarcinoma of the pancreas. This article provides an overview of the current treatment landscape of pancreatic cancer in Switzerland. In addition, we report a case of a long-term survivor with advanced pancreatic adenocarcinoma who achieved a notably good response to nal-IRI plus 5-FU/LV after progression on gemcitabine plus nab-paclitaxel.

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In Situ Formed ROS‐Responsive Hydrogel with STING Agonist and Gemcitabine to Intensify Immunotherapy against Pancreatic Ductal Adenocarcinoma

Wang

Huang

et al. 2023

Adv Healthcare Materials

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Immunotherapy, the most revolutionary anticancer strategy, faces major obstacles in yielding desirable outcomes in pancreatic ductal adenocarcinoma (PDAC) due to the highly immunosuppressive tumor microenvironment (TME). Meanwhile, when used alone, the traditional first‐line chemotherapeutic agent gemcitabine (GEM) in PDAC treatment is also insufficient to achieve lasting efficacy. In this study, a reactive oxygen species degradable hydrogel system, denoted as GEM‐STING@Gel, is engineered to codeliver gemcitabine and the stimulator of interferon genes (STING) agonist DMXAA (5,6‐dimethylxanthenone‐4‐acetic acid) into the tumor site. In this work, the strategy addresses the major challenges of current immunotherapies with a facile platform, which can synergistically activate innate immunity and promote the cytotoxic T lymphocytes infiltration at the tumor site, thereby modulating the immunosuppressive TME. Further, the efficient therapeutic potency of the immunotherapy is confirmed in an orthotopic postsurgical model, unleashing the translational potential to prevent tumor recurrence after surgical resection. This study underscores the advantages of this integrative strategy that combines chemotherapy, immunotherapy, and biomaterial‐based hydrogel, including improved therapeutic efficacy, operational convenience, and superior biosafety.

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Treatment landscape of metastatic pancreatic cancer

Cited by 126 publications

References 70 publications

Gene expression of cytokinesis regulators PRC1, KIF14 and CIT has no prognostic role in colorectal and pancreatic cancer

Gene expression of cytokinesis regulators PRC1, KIF14 and CIT has no prognostic role in colorectal and pancreatic cancer

Metastatic Pancreatic Cancer: Current Treatment Options for Swiss Patients

In Situ Formed ROS‐Responsive Hydrogel with STING Agonist and Gemcitabine to Intensify Immunotherapy against Pancreatic Ductal Adenocarcinoma

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