Anticancer effect of nucleoline-aptamer-conjugated gemcitabine loaded atellocollagen (IO401) in pancreatic cancer patient-derived orthotropic xenograft model

Smoking is highly associated with pancreatic cancer. Nicotine, the addictive component of tobacco, is involved in pancreatic cancer tumorigenesis, metastasis, and chemoresistance. This work aimed to describe the role of nicotine within the pancreatic cancer tumor microenvironment. Nicotine treatment was used in vitro to assess its effect on tumor-associated stromal cells and pancreatic cancer cells. Nicotine treatment was then used in a pancreatic cancer patient-derived xenograft model to study the effects in vivo. Nicotine induced secretion of interleukin 8 (IL-8) by tumor-associated stroma cells in an extracellular signal-regulated kinase (ERK)-dependent fashion. The secreted IL-8 and nicotine acted on the pancreatic cancer cell, resulting in upregulation of IL-8 receptor. Nicotine treatment of mice bearing pancreatic cancer patient-derived xenografts had significantly increased tumor mass, increased tumor-free weight loss, and decreased muscle mass. These represent important pathways through which nicotine acts within the tumor microenvironment and worsens pancreatic cancer-induced cachexia, potentially representing future therapeutic targets.

Download Full-text

Triple-Methyl Blockade With Recombinant Methioninase, Cycloleucine, and Azacitidine Arrests a Pancreatic Cancer Patient-Derived Orthotopic Xenograft Model

Pancreas ◽

10.1097/mpa.0000000000001709 ◽

2021 ◽

Vol 50 (1) ◽

pp. 93-98

Author(s):

Norihiko Sugisawa ◽

Jun Yamamoto ◽

Qinghong Han ◽

Yuying Tan ◽

Yoshihiko Tashiro ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patient ◽

Xenograft Model ◽

Pancreatic Cancer Patient ◽

Orthotopic Xenograft ◽

Orthotopic Xenograft Model

Download Full-text

Lorlatinib Induces Durable Disease Stabilization in a Pancreatic Cancer Patient with a ROS1 p.L1950F Mutation: Case Report

Oncology Research and Treatment ◽

10.1159/000517616 ◽

2021 ◽

pp. 1-7

Author(s):

Janna-Lisa Velthaus ◽

Peter Iglauer ◽

Ronald Simon ◽

Carsten Bokemeyer ◽

Peter Bannas ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patient ◽

Point Mutation ◽

Kinase Inhibitors ◽

Point Mutations ◽

Progression Free Survival ◽

Pancreatic Cancer Patient ◽

Targeted Treatment ◽

Precision Oncology ◽

Disease Stabilization

Introduction: The prognosis of pancreatic cancer has improved only modestly in recent years. This is partly due to the lack of development in precision oncology including immune oncology in this entity. Rearrangements of the proto-oncogene tyrosine protein kinase ROS1 gene represent driver alterations found especially in lung cancer. Tyrosine kinase inhibitors (TKI) with activity against ROS1 including lorlatinib substantially improved the outcome of this patient population. Anecdotal evidence reports treatment of pancreatic cancer harboring ROS1 fusions with ROS1 TKI, but data concerning treatment of patients with ROS1 point mutations are lacking. Case Presentation: This case describes a pancreatic cancer patient harboring a ROS1 point mutation that occurred without an underlying ROS1 rearrangement and thus not in the resistance situation. The heavily pretreated patient showed a strong decrease of the tumor biomarkers (CA19-9 and CEA) and radiologically a durable stable disease to the targeted treatment with lorlatinib, thereby achieving a progression-free survival of 12 months. Conclusion: Our data are the first to show a clinical benefit from targeted treatment with ROS1 TKI in a cancer patient with a thus far undescribed ROS1 point mutation without a concomitant ROS1 rearrangement. Furthermore, they indicate that ROS1 could be an oncogenic driver in pancreatic cancer. This subgroup could be eligible for targeted treatments, which may contribute to the urgently needed improvement in patient outcome.

Download Full-text