Study finds new way to make chemotherapy more effective against pancreatic cancer


ROCHESTER, Minn. — Pancreatic adenocarcinoma (PDAC) is a lethal malignancy that most often is resistant to chemotherapy. Researchers have been searching for ways to increase the sensitivity of the tumors to cancer-fighting drugs. A Mayo Clinic-led study published today opens a promising new front in that battle. Using patient cell lines and tumor-bearing models, researchers […]

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ConclusionsVCN-01 replicates and expresses hyaluronidase after intratumor injection both in preclinical models and in patients with pancreatic cancer. Enhanced chemotherapy access and reduction of tumor stiffness favours local control of pancreatic tumours treated with VCN-01 + standard of care.Clinical trial identificationEudraCT: 2012-005556-42.Legal entity responsible for the studyVCN Biosciences.FundingVCN Biosciences.DisclosureM. Hidalgo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory…

Source: Annals of OncologyCategory: Cancer & Oncology Source Type: research

AbstractBackgroundTumor Treating Fields (TTFields) are a non-invasive, antimitotic therapy delivered to the tumor via transducer arrays applied to the skin at tumor site. The only TTFields-related adverse event (AE) reported in clinical trials was localized dermatitis beneath the arrays. The safety of TTFields has also been investigated in glioblastoma, non-small-cell lung cancer (NSCLC), mesothelioma, pancreatic and ovarian cancer. This meta-analysis reported AEs in clinical studies with TTFields torso delivery.Methods192 patients from 4 pilot studies were included in the analysis: EF-15 (n  = 41, advanced N…

Source: Annals of OncologyCategory: Cancer & Oncology Source Type: research

A novel approach to sensitize tumor cells to chemotherapy is validated using patient ‐derived pancreatic cancer models, and investigation of corresponding molecular mechanism. The clinical candidate AXP107‐11 activates the G‐coupled estrogen receptor 1 (GPER1) enabling a novel therapeutic option to improve chemoefficacy in pancreatic cancer. AbstractDespite advances in cancer therapeutics, pancreatic cancer remains difficult to treat and often develops resistance to chemotherapies. We have evaluated a bioavailable genistein analogue, AXP107 ‐11 which has completed phase Ib clinical trial, as an approach to sensitiz…

Source: Cancer MedicineCategory: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research

In this study, we applied bioinformatics approaches, and integrated publicly available resources, to investigate the role of SMAD4 gene deletion in PDAC. We found that SMAD4 deletion was associated with poorer disease-free, but not overall, survival in PDAC patients. Cancer hallmark enrichment and pathway analysis suggested that the upregulation of cell cycle-related genes in SMAD4-deleted PDAC. Chemotherapy response profiling of PDAC cell lines and patient-derived organoids revealed that SMAD4-deleted PDAC was sensitive to gemcitabine, the first-line treatment for PDAC, and specific cell cycle-targeting drugs. Taken toget…

Source: GenesCategory: Genetics & Stem Cells Authors: Tags: Article Source Type: research

ConclusionCRS and HIPEC trend to improve survival. More studies need, not only to evaluate the role of HIPEC on malignant IPMN, but also prognosis and outcome.

Conclusions: These data identify a previously unknown role for GSK-3 kinases in the regulation of the TopBP1/ATR/Chk1 DNA damage response pathway. The data also support the inclusion of patients with PDAC in clinical studies of 9-ING-41 alone and in combination with gemcitabine.
PMID: 31533931 [PubMed – as supplied by publisher]

Source: Clinical Cancer ResearchCategory: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research

Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here…

Source: BMC CancerCategory: Cancer & Oncology Authors: Tags: Study protocol Source Type: research

More than eighty percent of pancreatic cancer involves ductal adenocarcinoma with an abundant desmoplastic extracellular matrix surrounding the solid tumor entity. This aberrant tumor microenvironment facilitates a strong resistance of pancreatic cancer to medication. Although various therapeutic strategies have been reported to be effective in mice with pancreatic cancer, they still need to be tested quantitatively in wider animal-based experiments before being applied as therapies. To aid the design of experiments, we develop a cell-based mathematical model to describe cancer progression under therapy w…

Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.
PMID: 31489036 [PubMed]

Source: JOPCategory: Gastroenterology Authors: Tags: Ther Adv Med Oncol Source Type: research

as Löhr

Clinical outcomes of chemotherapy for patients with advanced pancreatic adenocarcinoma in a real-world setting might differ from outcomes in randomized clinical trials (RCTs). Here we show in a single-institution cohort of 595 patients that median overall survival (OS) of patients who received gemcitabine alone (n = 185; 6.6 months (95% CI; 5.5–7.7)) was the same as in pivotal RCTs. Gemcitabine/capecitabine (n = 60; 10.6 months (95% CI; 7.8–13.3)) and gemcitabine/nab-paclitaxel (n = 66; 9.8 months (95% CI; 7.9–11.8)) resulted in a longer median OS and fluorouracil/oxaliplatin/…

Source: CancersCategory: Cancer & Oncology Authors: Tags: Article Source Type: research

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