Current concepts and novel targets in advanced pancreatic cancer

Abstract

Pancreatic cancer remains one of the most aggressive tumours with a 5-year survival rate of less than 5%. The dismal prognosis of this tumour entity that is associated with a high degree of drug resistance has not changed over the past decades. Since 1997, gemcitabine-based regimens have been the therapy of choice for advanced pancreatic cancer. Recently, however, new combination chemotherapy regimens achieved a significant survival benefit compared to gemcitabine-based therapies. In addition, novel approaches to improve drug delivery are currently being developed, and new drugs targeting signalling pathways both within the tumour cells and the tumour microenvironment are undergoing preclinical and clinical validation. Furthermore, efforts are being made to identify predictive markers for individualised treatment approaches based on molecular tumour characteristics. This review provides an overview on current and emerging concepts as well as novel targets for systemic treatment of advanced pancreatic cancer. Combination therapies incorporating drugs directed against these new targets may open new avenues for improving the efficacy of current treatment approaches and overcoming the devastating prognosis of pancreatic cancer patients.

Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL

“…In vivo experiments. To analyze the metastatic ability of MS cells in vivo, SUIT-2 cells (1x10 6 ) and MS cells (1x10 6 ) suspended in 100 ml DMeM were orthotopically transplanted into the 4-week-old female bALb/c nu/nu mice. At 5-7 weeks after implantation, we sacrificed the mice and all orthotopic tumors and livers were investigated.…”

“…Although efforts to reduce risk factors such as smoking, obesity, and high meat consumption and to improve early detection have been made, pancreatic cancer is still formidable because of its aggressive metastatic ability (3)(4)(5)(6). Pancreatic cancer mainly metastasizes to the lymph nodes, liver, lung, peritoneum and bone.…”

<i>In Vitro</i> Model Systems to Investigate Drug Resistance Mechanisms in Pancreatic Cancer Cells

“…While early detection of pancreatic cancer is critical to improve patient outcomes [4], there is an urgent need to develop more effective chemotherapies [5]. In 1997 gemcitabine (GEM), a nucleoside analog, replaced fluorouracil (5-FU) as the standard of care for patients with metastatic pancreatic cancer and continues to be the chemotherapeutic of choice to date [5] [6]. Since that time, different chemotherapeutic combination strategies have been used clinically with marginal effects on survivability [5].…”

“…A study of patients from [2002][2003][2004][2005][2006][2007][2008], shows that as many as 90% of the pancreatic cancers that could be staged had either regional or distant metastases at the time of diagnosis [2]. While early detection of pancreatic cancer is critical to improve patient outcomes [4], there is an urgent need to develop more effective chemotherapies [5]. In 1997 gemcitabine (GEM), a nucleoside analog, replaced fluorouracil (5-FU) as the standard of care for patients with metastatic pancreatic cancer and continues to be the chemotherapeutic of choice to date [5] [6].…”

“…In 1997 gemcitabine (GEM), a nucleoside analog, replaced fluorouracil (5-FU) as the standard of care for patients with metastatic pancreatic cancer and continues to be the chemotherapeutic of choice to date [5] [6]. Since that time, different chemotherapeutic combination strategies have been used clinically with marginal effects on survivability [5]. Most of these therapies have included gemcitabine as a chemotherapeutic backbone combined with another drug to enhance its effects [5] [7].…”