Role of C-Myc in the Development and Progression of Pancreatic Cancer

Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence, recurrence and mortality. C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer. Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells, promotes cell metabolism and proliferation, is an important factor driving the progress and maintenance of pancreatic cancer, and is related to chemotherapy and immunotherapy drug resistance. C-Myc also interacts with cell cyclin-dependent kinase(CDK) and non-coding RNA to regulate the proliferation, development and metastasis of pancreatic cancer. Therefore, targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer. The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’. Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc, inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box. However, direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer. C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc, C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc, thus affects the occurrence, development and metastasis of pancreatic cancer.