Evolving pancreatic cancer treatment: From diagnosis to healthcare management

Milella, Michèle; Bassi, Claudio; Boggi, Ugo; Brunetti, Oronzo; Cavaliere, Alessandro; Crippa, Stefano; Vita, Ferdinando De; Falconi, Massimo; Frassineti, Giovanni Luca; Giommoni, Elisa; Macchini, Marina; Malleo, Giuseppe; Silvestris, Nicola; Tudisco, Antonella; Vasile, Enrico; Reni, Michele

doi:10.1016/j.critrevonc.2021.103571

Cited by 20 publications

(13 citation statements)

References 180 publications

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“…Lastly, acquired resistance against cisplatin is multifactorial as demonstrated by Mecenzev et al, which is why further investigations are required to identify the underlying resistance mechanisms against cisplatin or oxaliplatin (as part of FOLFIRINOX regimen or as gemcitabine–cisplatin combination, that is used in several patients because it is less toxic than the FOLFIRINOX scheme) to further select patients for personal precision medicine [ 53 ]. Of note, this approach could also provide new tools for neoadjuvant chemotherapy, which is emerging as a potential strategy for the treatment of PDAC patients [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Biodegradable Ultrasmall-in-Nano Architectures Loaded with Cisplatin Prodrug in Combination with Ionizing Radiation Induces DNA Damage and Apoptosis in Pancreatic Ductal Adenocarcinoma

Pei

Mapanao

Gregori

et al. 2022

Cancers

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Considering the dismal survival rate, novel therapeutic strategies are warranted to improve the outcome of pancreatic ductal adenocarcinoma (PDAC). Combining nanotechnology for delivery of chemotherapeutics—preferably radiosensitizing agents—is a promising approach to enhance the therapeutic efficacy of chemoradiation. We assessed the effect of biodegradable ultrasmall-in-nano architectures (NAs) containing gold ultra-small nanoparticles (USNPs) enclosed in silica shells loaded with cisplatin prodrug (NAs-cisPt) combined with ionizing radiation (IR). The cytotoxic effects and DNA damage induction were evaluated in PDAC cell lines (MIA PaCa2, SUIT2-028) and primary culture (PDAC3) in vitro and in the chorioallantoic membrane (CAM) in ovo model. Unlike NAs, NAs-cisPt affected the cell viability in MIA PaCa2 and SUIT2-028 cells. Furthermore, NAs-cisPt showed increased γH2AX expression up to 24 h post-IR and reduced β-globin amplifications resulting in apoptosis induction at DNA and protein levels. Similarly, combined treatment of NAs-cisPt + IR in PDAC3 and SUIT2-028 CAM models showed enhanced DNA damage and apoptosis leading to tumor growth delay. Our results demonstrate an increased cytotoxic effect of NAs-cisPt, particularly through its release of the cisplatin prodrug. As cisplatin is a well-known radiosensitizer, administration of cisplatin prodrug in a controlled fashion through encapsulation is a promising new treatment approach which merits further investigation in combination with other radiosensitizing agents.

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Section: Discussionmentioning

confidence: 99%

Biodegradable Ultrasmall-in-Nano Architectures Loaded with Cisplatin Prodrug in Combination with Ionizing Radiation Induces DNA Damage and Apoptosis in Pancreatic Ductal Adenocarcinoma

Pei

Mapanao

Gregori

et al. 2022

Cancers

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“…Pancreatic cancer is one of the most lethal cancers worldwide [91,92]. The World Health Organization (WHO) estimates that in 2020 there were almost half a million new pancreatic cancer cases and almost half a million deaths due to pancreatic cancer.…”

Section: Pancreatic Cancermentioning

confidence: 99%

“…In fact, pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, has an overall survival in five years that does not exceed the 10%. PDAC incidence and mortality are increasing year by year making researchers believe that PDAC will become the second leading cause of cancer-related mortality by 2030 [91,92,94,95].…”

Section: Pancreatic Cancermentioning

confidence: 99%

“…Pancreatic tumors that extend beyond the pancreas or involve major vessels like the superior mesenteric artery or celiac axis are not considered safe for resection. Less than 20% of PDAC patients are eligible for surgery, and more than 75% of surgical treatments fail to eliminate all microscopically visible cancerous cells [91,92,96].…”

Section: Standard-of-care Treatment Of Pancreatic Cancermentioning

confidence: 99%

“…When resection of the tumor is not an option, chemotherapy remains the standard treatment with agents like gemcitabine plus nab-paclitaxel or FOLFIRINOX (5-fluorouracil, folinic acid, irinotecan plus oxaliplatin). Despite these treatments being useful, they present limited effects due to short-term response and toxicity, so there is still need for developing better treatments [91,92,94,96,97].…”

Section: Standard-of-care Treatment Of Pancreatic Cancermentioning

confidence: 99%

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Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System

Javed

Malagraba

Yarmohammadi

et al. 2022

Future Pharmacology

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Mitosis entails mechanistic changes required for maintaining the genomic integrity in all dividing cells. The process is intricate and temporally and spatially regulated by the ordered series of activation and de-activation of protein kinases. The mitotic kinases ensure the stepwise progression of entry into mitosis after the G2 phase of the cell cycle, followed by prophase, pro-metaphase, metaphase, anaphase, telophase, and subsequently cytokinesis and birth of two daughter cells with equal segregation and distribution of the genome. The major mitotic kinases include cyclin-dependent kinase 1 (CDK1), Aurora A and B Kinases, and Polo-Like-Kinase 1 (PLK1), among others. Overexpression of some of these kinases has been reported in many cancers as the mitotic fidelity and genome integrity are interlinked and dependent on these regulators, the native irregularities in these factors can be targeted as therapeutic strategies for various cancers. Here, we report and summarize the recent updates on the literature describing the various mitotic inhibitors targeting kinases, which can be used as potential therapeutic interventions for gastrointestinal cancers including gastric cancer, liver cancer, pancreatic cancer and colorectal cancer.

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“Depart from evil, and do good”: Turning Axl from uncontrolled tumorigenic gene to biomarker for early detection of pancreatic cancer

Comandatore

Balsano

Immordino

et al. 2022

Critical Reviews in Oncology/Hematology

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Evolving pancreatic cancer treatment: From diagnosis to healthcare management

Cited by 20 publications

References 180 publications

Biodegradable Ultrasmall-in-Nano Architectures Loaded with Cisplatin Prodrug in Combination with Ionizing Radiation Induces DNA Damage and Apoptosis in Pancreatic Ductal Adenocarcinoma

Biodegradable Ultrasmall-in-Nano Architectures Loaded with Cisplatin Prodrug in Combination with Ionizing Radiation Induces DNA Damage and Apoptosis in Pancreatic Ductal Adenocarcinoma

Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System

“Depart from evil, and do good”: Turning Axl from uncontrolled tumorigenic gene to biomarker for early detection of pancreatic cancer

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