Increased glucose availability sensitizes pancreatic cancer to chemotherapy.

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes.

Wild-type IDH1 inhibition enhances chemotherapy response in melanoma.

Background: Alternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme protects cancer cells under metabolic stress, including nutrient limited conditions in the tumor microenvironment.

Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors.

Nutrient-deprived conditions in the tumor microenvironment (TME) restrain cancer cell viability due to increased free radicals and reduced energy production. In pancreatic cancer cells a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables adaptation to these conditions. Under nutrient starvation, wtIDH1 oxidizes isocitrate to generate α-ketoglutarate (αKG) for anaplerosis and NADPH to support antioxidant defense.

Elucidating the Causes of Improved Survival in Clinical Trials of Randomized Adjuvant Pancreatic Ductal Adenocarcinoma (PDAC).

Background: Overall survival (OS) has increased in recent adjuvant clinical trials of pancreatic ductal adenocarcinoma (PDAC). Although oncologists have taken notice, the root causes have not been fully examined.

Methods: All phase 3 adjuvant PDAC clinical trials were screened (n = 13), and eight trials (2007-2019) that met a study requirement of having a gemcitabine monotherapy arm to serve as a uniform comparative anchor across trials were identified.

Is the Use of Intraoperative Frozen Section During Pancreaticoduodenectomy Justified?

Background: Intraoperative frozen section (IFS) is routinely utilized by many surgeons during pancreaticoduodenectomy. However, its utility has not been rigorously studied.

Methods: Patients who underwent pancreaticoduodenectomy between 2006 and 2015 were identified from institutional data.

Clinical Implications of Extensive Lymph Node Metastases for Resected Pancreatic Cancer.

Background: Outcomes of patients with resected pancreatic ductal adenocarcinoma (PDA) and extensive lymph node metastases have not been fully characterized.

Methods: A total of 637 patients underwent resection for pancreatic ductal adenocarcinoma (PDA) between 2002 and 2014 at the Thomas Jefferson University. Positive lymph node count (LNC) and positive lymph node ratio (LNR) were analyzed as predictors of cancer-specific outcomes, with a focus on outcomes of patients with extensive lymph node burden.