Pancreatic Cancer Treatment: Immunotherapy, Chemotherapy, Chemoradiation, and Targeted Therapy

Dear Colleagues,

Diagnosis of pancreatic cancer is an issue of grave concern and is tied to poor prognosis. Despite substantial progress in the molecular understanding of this tumor entity on different levels, including genetics and epigenetics, transcriptomics, oncogenic signaling, tumor metabolism, and tumor microenvironment, successful clinical translation, and thus, benefits to patients have been marginal. Emerging evidence suggests that cancer cells disseminate early on and remain dormant, eventually yielding micrometastases soon after surgical resection. Recognition of this phenomenon has given increasing merit to the application of therapeutic approaches targeting the entire organism (such as systemic chemotherapy) in cases of localized disease, in the form of neoadjuvant therapy. The introduction of (m)FOLFIRINOX combination chemotherapy has not only opened new avenues in palliative and adjuvant settings, but it also demonstrates remarkable neoadjuvant potency, enabling the downsizing and resection of locally advanced tumors, altering surgical strategies in the process. Furthermore, a first meaningful targeted therapy concept has been established with PARP inhibition as a maintenance therapy after first-line platinum-based chemotherapy for a small subgroup of patients with germline BRCA mutations. However, uncertainty remains on the ideal type(s) of locoregional and systemic therapy, the optimal doses, sequencing, and combination with other treatment modalities such as radiation, immunotherapy, and targeted therapies.

The continuous improvement in interdisciplinary care within multimodal therapeutic concepts and the implementation of personalized treatment approaches harnessing molecular insights will be vital for further substantial progress and meaningful impact on patients’ survival. As an example, the organoid-based, pharmacogenetically instructed stratification of induction, adjuvant, or palliative therapy concepts is currently being explored. Furthermore, the value of radiotherapy in neoadjuvant, intraoperative, and local recurrence settings awaits clarification.

This Special Issue aims to provide a platform for sharing the recent advancements in preclinical and clinical studies in the form of original studies, systematic reviews/meta-analyses, as well as review articles, pertaining to different treatment modalities in localized resectable, borderline resectable, locally advanced, or metastatic pancreatic cancer. This Special Issue will also focus on basic, translational, and clinical developments, highlighting interdisciplinary approaches, including neoadjuvant and adjuvant chemotherapy, (neo-) adjuvant and intraoperative radio- (chemo-) therapy, and targeted immunotherapy, as well as upcoming trends in treatment for pancreatic cancer. In addition, studies relating to the use of biomarkers to guide the best treatment approach in the form of personalized therapy and/or response to treatment are also welcome.

Dr. Constantinos Zambirinis
Dr. Brett Ecker
Guest Editors

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• pancreatic cancer
• pancreatic ductal adenocarcinoma
• actionable molecular mechanisms
• translational
• resection
• radiation therapy
• chemotherapy
• immunotherapy
• multimodal
• personalized medicine
• metastasis
• systemic therapy
• locoregional therapy
• KRAS inhibitors
• PARP inhibitors