Pancreatic cancer actionable genes in precision medicine and personalized surgery

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with an overall 5-year survival rate less than 5% due to the poor early diagnosis and lack of effective therapeutic options. The most effective therapy remains surgery, however post-operative survival could be enhanced with effective adjuvant therapy. The massive information gained from Omics techniques on PDAC at the beginning of the 21st century is a remarkable accomplishment. However, the information gained from the omics data, including next generation sequencing data, has yet to successfully affect care of patients suffering with PDAC. Therefore, we propose the development of an actionable genomic platform that matches a patient’s PDAC clinically actionable genes with potential targeted adjuvant therapies. Using this platform, PDX1 has been identified PDX1 as a potential actionable gene for PDAC, therefore, RNAi therapy, gene therapy and small inhibitory drugs, all targeting PDX1, serve as potential targeted adjuvant therapies. Preclinical studies support the hypothesis that identification of PDAC actionable genes could permit translation of a patient’s genomic information into precision targeted adjuvant therapy for PDAC.

The Crossroads of Precision Medicine and Therapeutic Decision-Making: Use of an Analytical Computational Platform to Predict Response to Cancer Treatments

“…Molecularly targeted cancer drugs are often developed with molecular diagnostics that attempt to identify which patients will achieve better outcomes on the new drug, and thus avoid innate treatment resistance. Such predictive biomarkers are playing an increasingly important role in precision oncology [10], but it is also recognized that the complexity of one patient's tumor cannot be sufficiently impacted by the use of a single marker/single-agent method.…”

Foundations for Molecular and Enzymatic Functional Surgery

“…Previously, the term "personalized surgery" was used exclusively to describe of the cancer treatment based on genetics data from patient [21] or the customized surgical treatment based on variant anatomy features [22]. Using a combination of coding (DNA, RNA) and signal (proteins and nucleic acids) molecules to regulate the body's functional for editing the genome and changing the cellular organization allows us to consider the possibility of personalizing surgical interventions based on the "omics" data of the patient's body (genome, epigenome, transcriptome, proteome, metabolome) to achieve an individual physiological response.…”

Foundations for Molecular and Enzymatic Functional Surgery

“…Previously, the term "personalized surgery" was used exclusively to describe of the cancer treatment based on genetics data from patient [21] or the customized surgical treatment based on variant anatomy features [22]. Clinical trials and training of "surgical team 2.0" will differ from the corresponding procedures when using of existing drugs and medical products.…”