Pancreatic cancer cachexia: three dimensions of a complex syndrome

Kordes, Maximilian; Larsson, Lars; Engstrand, Lars; Löhr, Matthias

doi:10.1038/s41416-021-01301-4

Cited by 37 publications

(42 citation statements)

References 200 publications

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“…Although inhibition of MLK1 by siRNA was shown to facilitate anti-proliferation effects in vitro using pancreatic cell lines [ 7 ], it is not clear whether using small molecules targeting MLK1 can suppress pancreatic cancers in an animal model. Moreover, it was of significance that mice treated with NSC14465 did not exhibit tumor-associated weight loss ( Figure 5 C), considering that cancer cachexia has wide ranging effects in patients with pancreatic cancer (63–64%) [ 33 ]. One possible explanation to the prevention of cancer cachexia-like weight loss is that NSC14465 effectively suppresses pancreatic cancer cells in the microenvironment in the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

Fan

Hsu

Lin

et al. 2021

Biology

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It was shown that mixed lineage kinase 1 (MLK1) regulates pancreatic cancer growth; however, its role in prostate cancer remains unclear. We showed that MLK1 is a tumor marker in prostate cancer by analyzing clinical gene expression data and identified a novel MLK1 inhibitor (NSC14465) from the compound library of the National Cancer Institute (NCI) using a MLK1 protein structure. The inhibitory effects of MLK1 were validated by an in vitro kinase assay and by monitoring phosphorylation signaling, and the anti-proliferation function was shown in several prostate and pancreatic cancer cell lines. We also demonstrated anti-tumor ability and prevention of cancer-related weight loss in a syngeneic orthotopic mouse model of pancreatic cancer that mimicked the tumor growth environment in the pancreas. Our results demonstrate that the MLK1 inhibitor is an anti-tumor agent for malignant prostate and pancreatic cancers.

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Section: Discussionmentioning

confidence: 99%

Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

Fan

Hsu

Lin

et al. 2021

Biology

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“…Due to the differences in the patient cohorts, assessment methodology, and diagnostic criteria used [22,23], the prevalence rates of CC and SC among PC patients are heterogeneous, ranging from 21.3 to 80% [4,5,22,24] and 28 to 89% [7,8,24], respectively. The largest cohort study including 977 PC patients using the same diagnostic criterion showed that 63% of patients were identified with CC, which was independently associated with worse OS but not related to all stages of disease, BMI classes, or receipt of chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

The Differential Clinical Impacts of Cachexia and Sarcopenia on the Prognosis of Advanced Pancreatic Cancer

Hou

Chen

Huang

et al. 2022

Cancers

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Pancreatic cancer (PC) has the highest frequency of developing cancer cachexia (CC)–sarcopenia (SC) syndrome, which negatively influences patients’ outcome, quality of life, and tolerance/response to treatments. However, the clinical impacts of CC, SC, and their associated factors on outcomes for advanced PC has yet to be fully investigated. A total of 232 patients were enrolled in this study for the retrospective review of their clinical information and the measurement of skeletal muscle areas at the third lumber vertebra by computed tomography scan to identify CC or SC. The association and concurrent occurrence of clinicopathological features in each patient, prevalence rates, and prognosis with the CC or SC were calculated. CC and SC were observed in 83.6% (n = 194) and 49.1% (n = 114) of PC patients, respectively. Low hemoglobin levels more often occurred in CC patients than in non-CC patients (p = 0.014). Older age (p = 0.000), female gender (p = 0.024), low body mass index (BMI) values (p = 0.004), low hemoglobin levels (p = 0.036), and low albumin levels (p = 0.001) were more often found in SC patients than in non-SC patients. Univariate and multivariate analyses showed that CC was an independent poor prognostic factor of overall survival (OS) and progression-free survival for all patients, the chemotherapy (C/T) subgroup, and the high BMI subgroup. Meanwhile, SC was an independent predictor of poor OS for the subgroups of C/T or high BMI but not for all patients. These findings reveal the clinical differences for CC and SC and provide useful information for predicting the prognosis of advanced PC patients and conducting personalized medicine.

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“…As a result, tumors that migrate to bone and release TGF-β result in poorer muscular force production regardless of whether muscle mass and body weight are reduced [74]. Also recognized that the activated conventional SMAD2/3 pathway promotes muscle fibrosis and ubiquitin ligase-mediated proteolysis while inhibiting Akt/mTOR-mediated tissue growth [75].…”

Section: Transforming Growth Factormentioning

confidence: 99%

Cytokines and Chemokines in Cancer Cachexia and Its Long-Term Impact on COVID-19

Singh

2022

Cells

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Cancer cachexia remains a serious public health concern worldwide, particularly as cancer rates rise. Treatment is endangered, and survival is reduced, because this illness is commonly misdiagnosed and undertreated. Although weight loss is the most evident sign of cachexia, there are other early metabolic and inflammatory changes that occur before the most obvious symptoms appear. Cachexia-related inflammation is induced by a combination of factors, one of which is the release of inflammation-promoting chemicals by the tumor. Today, more scientists are beginning to believe that the development of SARS-CoV-2 (COVID-19) related cachexia is similar to cancer-related cachexia. It is worth noting that patients infected with COVID-19 have a significant inflammatory response and can develop cachexia. These correlations provide feasible reasons for the variance in the occurrence and severity of cachexia in human malignancies, therefore, specific therapeutic options for these individuals must be addressed based on disease types. In this review, we highlighted the role of key chemokines, cytokines, and clinical management in relation to cancer cachexia and its long-term impact on COVID-19 patients.

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Pancreatic cancer cachexia: three dimensions of a complex syndrome

Cited by 37 publications

References 200 publications

Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

The Differential Clinical Impacts of Cachexia and Sarcopenia on the Prognosis of Advanced Pancreatic Cancer

Cytokines and Chemokines in Cancer Cachexia and Its Long-Term Impact on COVID-19

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