Targeting Defects in the Cellular DNA Damage Response for the Treatment of Pancreatic Ductal Adenocarcinoma

Schmitt, Anna; Feldmann, Georg; Zander, Thomas; Reinhardt, Hans Christian

doi:10.1159/000493401

Cited by 12 publications

(3 citation statements)

References 93 publications

(210 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Herein, we also evidenced that CBD and O 2 /O 3 , as single treatment or in combination, are able to reduce the expression of different genes of the PI3K pathway. PDAC, as above described, is also characterized by the acquisition of an anti-apoptotic phenotype, partially by inhibition of p53 and over-expression of anti-apoptotic proteins, which correlate with short survival and overall survival, particularly in Bcl-2 positive cases [ 55 , 56 ], and mutation in genes related to DNA damage response, such as BRCA1/2 [ 54 , 57 ]. Herein, we showed that CBD alone increased p53 and reduced BRCA2 gene expression.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Luongo¹,

Marinelli

Zeppa

et al. 2020

Cancers

View full text Add to dashboard Cite

Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.

show abstract

Section: Discussionmentioning

confidence: 99%

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Luongo¹,

Marinelli

Zeppa

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…For all this molecular evidence, ATM status analysis displays clinically relevant therapeutic implications. Indeed, similar to BRCA genetic alterations, ATM aberrations increase the efficacy of chemotherapeutic drugs which induce double strand DNA breaks, such as platinum drugs [67,68].…”

Section: Colloid Carcinomamentioning

confidence: 99%

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

Bazzichetto

Luchini

Cognetti

et al. 2020

IJMS

View full text Add to dashboard Cite

To date, pancreatic cancer is still one of the most lethal cancers in the world, mainly due to the lack of early diagnosis and personalized treatment strategies. In this context, the possibility and the opportunity of identifying genetic and molecular biomarkers are crucial to improve the feasibility of precision medicine. In 2019, the World Health Organization classified pancreatic ductal adenocarcinoma cancer (the most common pancreatic tumor type) into eight variants, according to specific histomorphological features. They are: colloid carcinoma, medullary carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, including also rhabdoid carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, hepatoid carcinoma, and signet-ring/poorly cohesive cells carcinoma. Interestingly, despite the very low incidence of these variants, innovative high throughput genomic/transcriptomic techniques allowed the investigation of both somatic and germline mutations in each specific variant, paving the way for their possible classification according also to specific alterations, along with the canonical mutations of pancreatic cancer (KRAS, TP53, CDKN2A, SMAD4). In this review, we aim to report the current evidence about genetic/molecular profiles of pancreatic cancer variants, highlighting their role in therapeutic and clinical impact.

show abstract

“…Several genetic predispositions and molecular alterations (31) have been found to be associated with this highly lethal entity. The most common mutated oncogenes in PAC and that were among the first to be reported in the literature are KRAS (32) and Bcl-2 (21), while p53 (33)(34)(35), deleted in pancreatic cancer 4 (21), cyclin-dependent kinase inhibitor 2 (CDKN2A) (17,35,36), retinoblastoma protein (17,21,33,34,36) are the most frequently deleted tumor suppressor genes. CDKN2A is a gene that encodes proteins involved in regulating the cell cycle, and mutations in this gene are commonly detected in PAC (36).…”

Section: Introductionmentioning

confidence: 99%

A pancreatic adenocarcinoma mimicking hepatoid carcinoma of uncertain histogenesis: A case report and literature review

Iliesiu,

Toma,

Ciongariu

et al. 2023

Oncol Lett

View full text Add to dashboard Cite

In rare cases, metastatic adenocarcinomas of different origin may exhibit the features of hepatoid carcinoma (HC), a rare malignant epithelial tumor, most commonly occurring in the ovaries and stomach, as well as in the pancreas and biliary ducts. A case of a 72-year-old female patient who developed a highly aggressive, poorly differentiated pancreatic ductal adenocarcinoma with peritoneal carcinomatosis, demonstrating hepatoid differentiation upon conventional hematoxylin and eosin staining is reported in the present study. The patient presented with severe abdominal pain, and the radiological investigations performed revealed ovarian and hepatic tumor masses and peritoneal lesions, which were surgically removed. The gross examination of the peritoneum and omentum revealed multiple solid, firm, grey-white nodules, diffusely infiltrating the adipose tissue. The microscopic examination revealed a malignant epithelial proliferation, composed of polygonal cells with abundant eosinophilic cytoplasm and irregular, pleomorphic nuclei. Certain cells presented with intracytoplasmic mucus inclusions, raising suspicion of a HC with an uncertain histogenesis. Immunohistochemical staining was performed, and the tumor cells were found to be positive for cytokeratin (CK)7, CK18 and mucin 5AC, whereas negative staining for CK20, caudal-type homeobox transcription factor 2, α-fetoprotein, paired box gene 8, GATA-binding protein 3 and Wilms tumor 1 were documented. Thus, the diagnosis of metastatic pancreatic adenocarcinoma was established. The main aim of the present study was to provide further knowledge concerning poorly differentiated metastatic adenocarcinoma resembling HC, emphasizing the histopathological and immunohistochemical features of these malignant lesions and raising awareness of the diagnostic difficulties that may arise, as well as the importance of the use immunohistochemistry in differentiating carcinomas of uncertain histogenesis.

show abstract

Targeting Defects in the Cellular DNA Damage Response for the Treatment of Pancreatic Ductal Adenocarcinoma

Cited by 12 publications

References 93 publications

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

A pancreatic adenocarcinoma mimicking hepatoid carcinoma of uncertain histogenesis: A case report and literature review

Contact Info

Product

Resources

About