Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy

Mukai, Yosuke; Yamada, Daisaku; Eguchi, Hidetoshi; Iwagami, Yoshifumi; Asaoka, Tadafumi; Noda, Takehiro; Kikuchi, Kôichi; Gotoh, Kunihito; Kobayashi, Shogo; Takeda, Yutaka; Tanemura, Masahiro; Mori, Masaki; Doki, Yuichiro

doi:10.1245/s10434-018-6431-8

Cited by 33 publications

(25 citation statements)

References 28 publications

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“…The beneficial effects of vitamin D supplementation on the survival of PDAC patients have been attributed not only to its direct anticancer effects [13], but also to its effects on the tumor microenvironment. In patients undergoing pre-operative chemoradiotherapy, Mukai et al demonstrated that distant metastases-free survival was longer in those with higher than in those with lower levels of vitamin D, which, according to the authors, acts by suppressing the activation of CAFs [14]. In agreement, Sherman et al demonstrated that vitamin D receptor engagement acts as a master transcriptional regulator of PSCs and, in association with standard gemcitabine treatment, prolongs survival in genetically engineered mice [15].…”

Section: Introductionmentioning

confidence: 90%

Vitamin D Prevents Pancreatic Cancer-Induced Apoptosis Signaling of Inflammatory Cells

et al. 2020

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Combined approaches based on immunotherapy and drugs supporting immune effector cell function might increase treatment options for pancreatic ductal adenocarcinoma (PDAC), vitamin D being a suitable drug candidate. In this study, we evaluated whether treatment with the vitamin D analogue, calcipotriol, counterbalances PDAC induced and SMAD4-associated intracellular calcium [Ca2+]i alterations, cytokines release, immune effector function, and the intracellular signaling of peripheral blood mononuclear cells (PBMCs). Calcipotriol counteracted the [Ca2+]i depletion of PBMCs induced by SMAD4-expressing PDAC cells, which conditioned media augmented the number of calcium flows while reducing whole [Ca2+]i. While calcipotriol inhibited spontaneous and PDAC-induced tumor necrosis factor alpha (TNF-α) release by PBMC and reduced intracellular transforming growth factor beta (TGF-β), it did not counteract the lymphocytes proliferation induced in allogenic co-culture by PDAC-conditioned PBMCs. Calcipotriol mainly antagonized PDAC-induced apoptosis and partially restored PDAC-inhibited NF-κB signaling pathway. In conclusion, alterations induced by PDAC cells in the [Ca2+]i of immune cells can be partially reverted by calcipotriol treatment, which promotes inflammation and antagonizes PBMCs apoptosis. These effects, together with the dampening of intracellular TGF-β, might result in an overall anti-tumor effect, thus supporting the administration of vitamin D in PDAC patients.

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Section: Introductionmentioning

confidence: 90%

Vitamin D Prevents Pancreatic Cancer-Induced Apoptosis Signaling of Inflammatory Cells

et al. 2020

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“…In addition, the relationship among VD, VD receptor (VDR) and prognosis of PDAC were reported. Investigators demonstrated that low expression of VDR or low circulating VD level (<20 ng/ml) was related to a poor prognosis of PDAC ( 185 – 187 ). Gene expression profiling studies demonstrated that PSCs showed a strong expression of VDR ( 137 ).…”

Section: Current Progress In Targeting Strategiesmentioning

confidence: 99%

The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives

Zhang

Jiang

et al. 2021

Front. Oncol.

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Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal malignancy with a dismal clinical outcome. Accumulating evidence suggests that activated pancreatic stellate cells (PSCs), the major producers of extracellular matrix (ECM), drive the severe stromal/desmoplastic reaction in PDAC. Furthermore, the crosstalk among PSCs, pancreatic cancer cells (PCCs) as well as other stroma cells can establish a growth-supportive tumor microenvironment (TME) of PDAC, thereby enhancing tumor growth, metastasis, and chemoresistance via various pathways. Recently, targeting stroma has emerged as a promising strategy for PDAC therapy, and several novel strategies have been proposed. The aim of our study is to give a profound review of the role of PSCs in PDAC progression and recent advances in stroma-targeting strategies.

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“…Higher levels of blood 25-hydroxyvitamin D [25(OH)D] are associated with longer survival duration in patients with PC [ 14 ]. Experimental evidence indicates that vitamin D exerts anticancer effects by inhibiting cancer cell proliferation, inducing apoptosis and differentiation and potentiating chemo- or radiotherapy in various cancers [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Interestingly, experimental data also demonstrate that vitamin D regulates the tumor microenvironment, particularly cancer-associated fibroblast reprogramming, to facilitate tumor repression [ 20 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D: Promises on the Horizon and Challenges Ahead for Fighting Pancreatic Cancer

Wei

Wang

Zuo

et al. 2021

Cancers

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Pancreatic cancer has a dismal prognosis, while its incidence is increasing. This is attributed, in part, to a profound desmoplastic and immunosuppressive tumor microenvironment associated with this cancer and resistance to current available therapies. Novel and effective intervention strategies are urgently needed to improve the outcomes of patients with pancreatic cancer. Vitamin D has pleiotropic functions beyond calcium–phosphate homeostasis and has been extensively studied both in the laboratory and clinic as a potential preventive agent or adjunct to standard therapies. Accumulating evidence from ecological, observational, and randomized controlled trials suggests that vitamin D has beneficial effects on risk, survival, and mortality in pancreatic cancer, although controversies still exist. Recent advances in demonstrating the important functions of vitamin D/vitamin D receptor (VDR) signaling in the regulation of stromal reprogramming, the microbiome, and immune response and the emergence of checkpoint immunotherapy provide opportunities for using vitamin D or its analogues as an adjunct for pancreatic cancer intervention. Many challenges lie ahead before the benefits of vitamin D can be fully realized in pancreatic cancer. These challenges include the need for randomized controlled trials of vitamin D to assess its impact on the risk and survival of pancreatic cancer, optimizing the timing and dosage of vitamin D or its analogues as an adjunct for pancreatic cancer intervention and elucidating the specific role of vitamin D/VDR signaling in the different stages of pancreatic cancer. Nevertheless, vitamin D holds great promise for reducing risk and improving outcomes of this disease.

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Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy

Abstract: In conjunction with established current therapies, vitamin D supplementation may be an effective treatment for PDAC patients by inactivating CAFs.

Cited by 33 publications

References 28 publications

Vitamin D Prevents Pancreatic Cancer-Induced Apoptosis Signaling of Inflammatory Cells

Vitamin D Prevents Pancreatic Cancer-Induced Apoptosis Signaling of Inflammatory Cells

The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives

Vitamin D: Promises on the Horizon and Challenges Ahead for Fighting Pancreatic Cancer

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