Moving Towards Dawn: KRas Signaling and Treatment in Pancreatic
Ductal Adenocarcinoma

Tarun      Rajpurohit; Sankha      Bhattacharya
Abstract

“Pancreatic ductal adenocarcinoma (PDAC)” is robust, nearly clueless, and all-around deadly among all tumors. Below 10 %, the general 5-year endurance period has remained adamantly unaltered in the last 30 years, regardless of enormous clinical and therapeutic endeavors. The yearly number of deaths is more than the number of recently analyzed cases. Not a classic one, but “Carbohydrate Antigen CA19- 9” remains the prevailing tool for diagnosis. MicroRNAs and non-invasive techniques are now incorporated for the effective prognosis of PDAC than just CA19-9. Mutated “Rat sarcoma virus Ras” conformation “V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRas” is 95 % accountable for PDAC, and its active (GTP-bound) formation activates signaling cascade comprising “Rapidly accelerated fibrosarcoma Raf”/“Mitogen-activated protein kinase MEK”/ “Extracellular signal-regulated kinase ERK” with “Phosphoinositide 3-kinase PI3K”/ “protein kinase B Akt”/ “mammalian target of rapamycin mTOR” pathways. KRas has acquired the label of ‘undruggable’ since the crosstalk in the nexus of pathways compensates for Raf and PI3K signaling cascade blocking. It is arduous to totally regulate KRascoordinated PDAC with traditional medicaments like “gemcitabine GEM” plus nabpaclitaxel/ FOLFIRINOX. For long-haul accomplishments aiming at KRas, future endeavors should be directed to combinatorial methodologies to adequately block KRas pathways at different standpoints. Currently they are contributing to healing PDAC. In this review article, we outline the function of KRas in carcinogenesis in PDAC, its signaling cascade, former techniques utilized in hindering Kras, current and future possibilities for targeting Kras.
Keywords: KRas, PDAC, pancreatic cancer, Akt, Raf, PI3K, MEK, G12D.
Graphical Abstract

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DOI https://dx.doi.org/10.2174/1874467215666220128161647	Print ISSN 1874-4672
Publisher Name Bentham Science Publisher	Online ISSN 1874-4702
Current Molecular Pharmacology

Moving Towards Dawn: KRas Signaling and Treatment in Pancreatic Ductal Adenocarcinoma

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