TY - JOUR
T1 - Acinar to ductal cell trans-differentiation
T2 - A prelude to dysplasia and pancreatic ductal adenocarcinoma
AU - Parte, Seema
AU - Nimmakayala, Rama Krishna
AU - Batra, Surinder K.
AU - Ponnusamy, Moorthy P.
N1 - Funding Information:
The authors/work in this article were supported, in parts, by the following grants from the National Institutes of Health ( P01 CA217798 , R01 CA210637 and R01 CA195586 ) and the Nebraska Department of Health and Human Services LB595 .
Publisher Copyright:
© 2021
PY - 2022/1
Y1 - 2022/1
N2 - Pancreatic cancer (PC) is the deadliest neoplastic epithelial malignancies and is projected to be the second leading cause of cancer-related mortality by 2024. Five years overall survival being ~10%, mortality and incidence rates are disturbing. Acinar to ductal cell metaplasia (ADM) encompasses cellular reprogramming and phenotypic switch-over, making it a cardinal event in tumor initiation. Differential cues and varied regulatory factors drive synchronous functions of metaplastic cell populations leading to multiple cell fates and physiological outcomes. ADM is a precursor for developing early pre-neoplastic lesions further progressing into PC due to oncogenic signaling. Hence delineating molecular events guiding tumor initiation may provide cues for regenerative medicine and precision onco-medicine. Therefore, understanding PC pathogenesis and early diagnosis are crucial. We hereby provide a timely overview of the current progress in this direction and future perspectives we foresee unfolding in the best interest of patient well-being and better clinical management of PC.
AB - Pancreatic cancer (PC) is the deadliest neoplastic epithelial malignancies and is projected to be the second leading cause of cancer-related mortality by 2024. Five years overall survival being ~10%, mortality and incidence rates are disturbing. Acinar to ductal cell metaplasia (ADM) encompasses cellular reprogramming and phenotypic switch-over, making it a cardinal event in tumor initiation. Differential cues and varied regulatory factors drive synchronous functions of metaplastic cell populations leading to multiple cell fates and physiological outcomes. ADM is a precursor for developing early pre-neoplastic lesions further progressing into PC due to oncogenic signaling. Hence delineating molecular events guiding tumor initiation may provide cues for regenerative medicine and precision onco-medicine. Therefore, understanding PC pathogenesis and early diagnosis are crucial. We hereby provide a timely overview of the current progress in this direction and future perspectives we foresee unfolding in the best interest of patient well-being and better clinical management of PC.
KW - Acinar-ductal metaplasia
KW - PDAC
KW - Pancreatic cancer initiation
KW - Preneoplastic pancreatic lesions
KW - Trans-differentiation
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U2 - 10.1016/j.bbcan.2021.188669
DO - 10.1016/j.bbcan.2021.188669
M3 - Review article
C2 - 34915061
AN - SCOPUS:85121467865
SN - 0304-419X
VL - 1877
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 1
M1 - 188669
ER -