Targeting Pancreatic Cancer: Strategies and Hopes

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Background

Pancreatic cancer is one of the deadly cancers in the world. Despite the advances in the field of cancer research and therapeutic strategies, Pancreatic cancer remains among the most difficult to treat cancers with a 5 years survival of less than 5%. Mostly, pancreatic cancers will be arising from pancreatic intraepithelial neoplasia, a microscopic non-invasive epithelial growth in the pancreatic ducts. Surgical removal is the only potential treatment, and adjuvant chemo therapies using Gemcitabine, S1 and oral fluoropyrimidine derivative also can be given for the patient. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) also being used for the patients, who are not eligible for surgery. But so far, the response rate shown by pancreatic cancer is very poor to any cytotoxic drug leading to poor prognosis.

The major reason for the exceptional lethality is the asymptomatic nature at the preliminary stage. Development of a screening test to detect the pancreatic cancers as early as possible is essential in order to curb the mortality rate.

To date there is no targetable driver genes or gene mutations have been recognised. KRAS is the most prominent mutation found in more than 95% of pancreatic cancers. ( 29229669). KRAS mutation makes a permanent activation of RAS signalling leading to persistent activation of genes involved in proliferation, survival,
transformation and migration. Other major mutations occurring in pancreatic cancers are mutation of TP53(64%) SMAD 4(21%), and CDKN2A(17%). Among them, P53 shows inactivation mutation which causes loss of control on cell division and mismatch repair. SMAD4 mutation also helps pancreatic cancer transformation by inducing migration/invasion properties. CDKN2A show a universal loss of function caused by missense mutations and in-transgenic or homozygous deletion mutations and promoter methylation (encoding p16INK4A and p19ARF), together with promoter silencing in PDAC.

Recent development in Cancer therapies including new targeted therapies and Immunotherapy giving some hope in improvement in the treatment efficacies of Pancreatic Cancer. The new attempts to target KRAS and SMAD4 are also gaining scientific attention recently. New information on the existence of Cancer stem cells and possibility of targeting cancer stem cells also helping to develop new strategies in the fast moving world. It is necessary to assess the recent scientific
advancement in this specific are of Pancreatic cancer research, which will help the scientific world to know more about the recent research strategies and hopes.

This Research Topic will be focused on the latest trends in pancreatic cancer research, discuss new strategies in therapy development and their hope to help the patients. We welcome Original Research and Review articles addressing, but not limited to, the following themes:

1. Pancreatic cancer diagnosis, therapy resistance, and therapy interventions such as combination therapy and nano-particle lead therapies
2. Drug designing and discovery
3. Preclinical and Clinical modelling
4. Signalling pathway tracing including RAS signalling and involvement of cancer stem cells
5. Genomics of pancreatic cancer, including microRNA signatures and genetic predispositions for disease prediction

Keywords: pancreatic cancer, kras, smad4, rad, tp53, folfirinox

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