Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer

Abstract

The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences disease relapse, even when a combination adjuvant therapy is offered. Therefore, aiming at improving disease free survival and overall survival of these patients, there is an increasing interest in evaluating the activity and efficacy of neoadjuvant and perioperative treatments. In this view, it is of utmost importance to find biomarkers able to select patients who may benefit from a preoperative therapy rather than upfront surgical resection. Defined genomic alterations and a dynamic inflammatory microenvironment are the major culprits for disease recurrence and resistance to chemotherapeutic treatments in pancreatic cancer patients. Signal transduction pathways or tumor immune microenvironment could predict early recurrence and response to chemotherapy. In the last decade, distinct molecular subtypes of pancreatic cancer have been described, laying the bases to a tailored therapeutic approach, started firstly in the treatment of advanced disease. Patients with homologous repair deficiency, in particular with mutant germline BRCA genes, represent the first subgroup demonstrating to benefit from specific therapies. A fraction of patients with pancreatic cancer could take advantage of genome sequencing with the aim of identifying possible targetable mutations. These genomic driven strategies could be even more relevant in a potentially curative setting. In this review, we outline putative predictive markers that could help in the next future in tailoring the best therapeutic strategy for pancreatic cancer patients with a potentially curable disease.

Neoadjuvant therapy in resectable pancreatic cancer: A promising curative method to improve prognosis

“…It is essential to select patients who could mostly benefit from NAT. Some novel predictive factors in R-PA were addressed recently, such as molecular profiles, tumor microenvironments, immune cell infiltration, microRNAs, circulating tumor DNA, organoids, and the gut microbiome[ 48 ]. In the future, the RCT study design should likely be refined in patients with three types of resectable PC.…”

Genetics, Genomics and Emerging Molecular Therapies of Pancreatic Cancer

“…Therefore, genome-wide studies are crucial for understanding the contribution of variable genetic mutations to the carcinogenesis, progression and metastasis of pancreatic cancer in order to offer a personalised medicine approach by providing implications for further clinical achievements and drug development [21,38]. Unfortunately, the molecular characterisation in pancreatic cancer is not yet standard in clinical care, but great efforts are being made to use multiple insights provided by recent NGS-based studies in clinical trials [39]. According to Felsenstein et al, genetic alterations may be used to develop diagnostic markers for early detection, disease progression and novel targeted therapies [25].…”

“…The results obtained in this study enabled the selection of patients receiving a molecularly targeted matched therapy. Inconveniently, this genomic profiling method may be used only when standard treatments fail and in young patients with a good performance status [39,45].…”

Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?

“…Similarly, many PDAC patients have distant metastatic disease at presentation, with the majority being hepatic due to the portal drainage of the pancreas [27][28][29], and current international practice guidelines advise against resection of PDAC in the setting of liver metastases [30][31][32][33][34]. Should the tumour be resectable and the patient receive systemic therapy, 5-year survival can reach up to 30% [35].…”