The KRAS proto-oncogene is a major driver of pancreatic tumorigenesis and is nearly ubiquitously mutated in pancreatic ductal adenocarcinoma (PDAC). KRAS point mutations are detected in over 90% of PDAC cases, and these mutations have been shown to be associated with worse therapy response and overall survival. Pathogenic KRAS mutations are mostly limited to codons 12, 13 and 61, with G12D, G12V, G12R, Q61H, and G13D accounting for approximately 95% of the mutant cases. Emerging data have shown the importance of specific mutant subtypes, as well as KRAS variant allele frequency on clinical prognosis. Furthermore, novel technologies and therapies are being developed to target specific mutant subtypes, with encouraging early results. In this paper, we aim to review the recent studies regarding the relative impact of specific mutant KRAS subtypes on oncologic outcomes, the application of variant allele frequency in next generation sequencing analyses, and the ongoing research into therapies targeting specific mutant KRAS subtypes.

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM.

Obesity is a risk factor for pancreatic cancer which may be treated with Roux-en-Y gastric bypass and represents an increasing morbidity. Post-RYGB anatomy poses considerable challenges for reconstruction after pancreaticoduodenectomy (PD), a growing problem encountered by surgeons. We characterize specific strategies used for post-PD reconstruction in the RYGB patient. PubMed search was performed using MeSH terms “Gastric Bypass” and “Pancreaticoduodenectomy” between 2000 and 2018. Articles reporting cases of pancreaticoduodenectomy in post-RYGB patients were included and systematically reviewed for this study. Three case reports and five case series (25 patients) addressed PD after RYGB; we report one additional case. The typical post-gastric bypass PD patient is a woman in the sixth decade of life, presenting most commonly with pain (69.2%) and/or jaundice (53.8%), median 5 years after RYGB. Five post-PD reconstructive options are reported. Among these, the gastric remnant was resected in 18 cases (69.2%), with reconstruction of biliopancreatic drainage most commonly achieved using the distal jejunal segment of the pre-existing biliopancreatic limb (73.1%). Similarly, in the eight cases where the gastric remnant was spared (30.8%), drainage was most commonly performed using the distal jejunal segment of the biliopancreatic limb (50%). Among the 17 cases reporting follow-up data, median was 27 months. Reconstruction options after PD in the post-RYGB patient focus on resection or preservation gastric remnant, as well as creation of new biliopancreatic limb. Insufficient data exists to make recommendations regarding the optimal reconstruction option, yet surgeons must prepare for the possible clinical challenge. PD reconstruction post-RYGB requires evaluation through prospective studies.

In this editorial, we highlight articles published in this Special Issue of Vaccines on “Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment”, recent developments in the field of cancer vaccines, and the potential for immunotherapeutic combinations in cancer care. This issue covers important developments and progress being made in the cancer vaccine field and possible future directions for exploring new technologies to produce optimal immune responses against cancer and expand the arena of prophylactic and therapeutic cancer vaccines for the treatment of this deadly disease.