Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma

Abstract

Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor-specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under-addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.

An Emerging Role for the Unfolded Protein Response in Pancreatic Cancer

“…Historically, the standard-of-care chemotherapy for PDAC was gemcitabine. However, first line therapies now tend to be FOLFIRINOX (a combination of oxaliplatin, irinotecan, 5-fluorouracil and leucovorin) or a combination of gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel [ 5 ]. Although chemotherapeutic intervention can improve survival of patients with early-stage pancreatic cancer, these treatments grant limited benefits to patients with late stages of the disease who have short life expectancies [ 6 ].…”

“…The TME can occupy up to 90% of the entire tumour mass and comprises both cellular and acellular components [ 5 ]. High stromal content in PDAC is a consequence of the activity of cancer associated fibroblasts (CAFs) resulting in increased deposition of extracellular matrix (ECM) components [ 13 ].…”

The RNA methyltransferase NSUN6 suppresses pancreatic cancer development by regulating cell proliferation

“…Pancreatic cancer (PC) is a highly aggressive solid tumor with a 5-year survival of less than 10%, and with incidence rates increased during the past decade [1] . Despite the knowledge about PC still increasing, mechanisms involving in PC development remain unclear, and more effective therapies await discovery [2] , [3] , [4] .…”

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

“…With the annual increase in pancreatic cancer-related deaths, it is estimated that by 2030, just a decade from now, malignant tumors will be the second leading cause of cancer-related deaths in the United States[ 4 ]. Based on the latest data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute, the 5-year overall survival (OS) rate for pancreatic cancer patients is only 10% in the United States[ 5 , 6 ]. At present, radical surgical resection is still an important method, or even the only way, to prolong significantly the survival time of pancreatic cancer patients[ 7 ].…”

“…At present, radical surgical resection is still an important method, or even the only way, to prolong significantly the survival time of pancreatic cancer patients[ 7 ]. Nevertheless the 5-year OS rate of patients undergoing radical resection is still less than 20%[ 8 , 9 ], despite the concept of surgery-based comprehensive treatment being constantly practiced and updated in clinical work[ 6 ]. Moreover, only 20% of patients diagnosed with pancreatic cancer have access to surgical treatment[ 10 ].…”