Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention

Stoffel, Elena M.; Brand, Randall E.; Goggins, Michael

doi:10.1053/j.gastro.2023.02.012

Cited by 68 publications

(51 citation statements)

References 119 publications

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“…We retrospectively assessed 32 patients with historically diagnosed PDAC in Ruijin Hospital and written informed consent was obtained. We included patients that met the following two criteria: (1) Standardized Clinical Biobank in our hospital. All patients with neuroendocrine, duodenal, distal-bile duct, and ampullary carcinoma were excluded.…”

Section: Patientsmentioning

confidence: 99%

The inverted U‐shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte

Li,

Zhu,

Deng

2024

Cancer Medicine

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BackgroundThe relationship between epinephrine and cancer can be dose‐dependent in in vivo study. Whether it is the same in human body still needs verification.MethodWe used frozen human pancreatic ductal adenocarcinoma (PDAC) tissues to detect epinephrine content and analyzed its relationship with survival using the K‐M method and Cox regression. Disturbance of blood cell count and C‐reactive protein and identification of related potent intermediary factors were also analyzed.ResultsK‐M plot and Cox regression all showed the inverted U‐shaped relationship between epinephrine and PDAC survival. Lymphocyte adjustment can increase the HRs of epinephrine for PDAC death by >10%.ConclusionEpinephrine played an anti‐tumor or pro‐tumor effect depending on the specific concentration. Circulating lymphocyte count was elevated and might acted as a compensation pathway to reduce the pro‐tumor effect of epinephrine to PDAC.

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Section: Patientsmentioning

confidence: 99%

The inverted U‐shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte

Li,

Zhu,

Deng

2024

Cancer Medicine

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“…1 PC is the seventh leading cause of cancer-related deaths worldwide and is predicted to surpass lung, prostate, breast, colorectal, and bladder carcinoma to become the second foremost cause of cancer-related death by 2030. 2,3 The median 5-year survival rate is lowest in PC patients, i.e., 10%-11%, due to delay in the early diagnosis and inadequate response to chemotherapy. 4,5 The foremost reason for the poor survival rate in most PC patients is diagnosis at advanced stages of disease (>80%) at which the tumor already acquired metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…This limits the option of tumor removal through surgical resection in up to 20% of cases, and among them, overall survival is better in only stage 1 and node-negative patients. 3 The presently available neoadjuvant therapy regimens such as a combination of FOLFIRINOX (folinic acid, 5-fluorouracil , irinotecan, and oxaliplatin), 5-FU, albuminbound paclitaxel (nab-paclitaxel) plus gemcitabine provides a diseasefree survival up to 6-30 months in PC patients and do not completely eradicate the tumor. 4,[6][7][8] Cancer stem cells and senescent or therapyresistant cancer cells make it challenging to achieve a pathological complete response in PC patients.…”

Section: Introductionmentioning

confidence: 99%

“…Pancreatic cancer (PC) is highly aggressive due to higher invasiveness, metastasis, chemoresistance, and disease relapse 1 . PC is the seventh leading cause of cancer‐related deaths worldwide and is predicted to surpass lung, prostate, breast, colorectal, and bladder carcinoma to become the second foremost cause of cancer‐related death by 2030 2,3 . The median 5‐year survival rate is lowest in PC patients, i.e., 10%–11%, due to delay in the early diagnosis and inadequate response to chemotherapy 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…The foremost reason for the poor survival rate in most PC patients is diagnosis at advanced stages of disease (>80%) at which the tumor already acquired metastasis. This limits the option of tumor removal through surgical resection in up to 20% of cases, and among them, overall survival is better in only stage 1 and node‐negative patients 3 . The presently available neoadjuvant therapy regimens such as a combination of FOLFIRINOX (folinic acid, 5‐fluorouracil [5‐FU], irinotecan, and oxaliplatin), 5‐FU, albumin‐bound paclitaxel (nab‐paclitaxel) plus gemcitabine provides a disease‐free survival up to 6–30 months in PC patients and do not completely eradicate the tumor 4,6–8 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of bio‐flavonols and their derivatives in improving mitochondrial dysfunctions associated with pancreatic tumorigenesis

Sharma,

Arora,

Bansal

et al. 2024

Cell Biochemistry & Function

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Mitochondria, a cellular metabolic center, efficiently fulfill cellular energy needs and regulate crucial metabolic processes, including cellular proliferation, differentiation, apoptosis, and generation of reactive oxygen species. Alteration in the mitochondrial functions leads to metabolic imbalances and altered extracellular matrix dynamics in the host, utilized by solid tumors like pancreatic cancer (PC) to get energy benefits for fast‐growing cancer cells. PC is highly heterogeneous and remains unidentified for a longer time because of its complex pathophysiology, retroperitoneal position, and lack of efficient diagnostic approaches, which is the foremost reason for accounting for the seventh leading cause of cancer‐related deaths worldwide. PC cells often respond poorly to current therapeutics because of dense stromal barriers in the pancreatic tumor microenvironment, which limit the drug delivery and distribution of antitumor immune cell populations. As an alternative approach, various natural compounds like flavonoids are reported to possess potent antioxidant and anticancerous properties and are less toxic than current chemotherapeutic drugs. Therefore, we aim to summarize the current state of knowledge regarding the pharmacological properties of flavonols in PC in this review from the perspective of mitigating mitochondrial dysfunctions associated with cancer cells. Our literature survey indicates that flavonols efficiently regulate cellular metabolism by scavenging reactive oxygen species, mitigating inflammation, and arresting the cell cycle to promote apoptosis in tumor cells via intrinsic mitochondrial pathways. In particular, flavonols proficiently inhibit the cancer‐associated proliferation and inflammatory pathways such as EGFR/MAPK, PI3K/Akt, and nuclear factor κB in PC. Overall, this review provides in‐depth evidence about the therapeutic potential of flavonols for future anticancer strategies against PC; still, more multidisciplinary human interventional studies are required to dissect their pharmacological effect accurately.

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Nrf2‐mediated adenylosuccinate lyase promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma cells through ferroptosis escape

Hsu,

Wang,

Chen

et al. 2024

Journal Cellular Physiology

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Pancreatic cancer has one of the highest fatality rates and the poorest prognosis among all cancer types worldwide. Gemcitabine is a commonly used first‐line therapeutic drug for pancreatic cancer; however, the rapid development of resistance to gemcitabine treatment has been observed in numerous patients with pancreatic cancer, and this phenomenon limits the survival benefit of gemcitabine. Adenylosuccinate lyase (ADSL) is a crucial enzyme that serves dual functions in de novo purine biosynthesis, and it has been demonstrated to be associated with clinical aggressiveness, prognosis, and worse patient survival for various cancer types. In the present study, we observed significantly lower ADSL levels in gemcitabine‐resistant cells (PANC‐1/GemR) than in parental PANC‐1 cells, and the knockdown of ADSL significantly increased the gemcitabine resistance of parental PANC‐1 cells. We further demonstrated that ADSL repressed the expression of CARD‐recruited membrane‐associated protein 3 (Carma3), which led to increased gemcitabine resistance, and that nuclear factor erythroid 2‐related factor 2 (Nrf2) regulated ADSL expression in parental PANC‐1 cells. These results indicate that ADSL is a candidate therapeutic target for pancreatic cancer involving gemcitabine resistance and suggest that the Nrf2/ADSL/Carma3 pathway has therapeutic value for pancreatic cancer with acquired resistance to gemcitabine.

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Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention

Cited by 68 publications

References 119 publications

The inverted U‐shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte

The inverted U‐shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte

Role of bio‐flavonols and their derivatives in improving mitochondrial dysfunctions associated with pancreatic tumorigenesis

Nrf2‐mediated adenylosuccinate lyase promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma cells through ferroptosis escape

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