TY - JOUR
T1 - Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC)
AU - Chandana, S. R.
AU - Babiker, H. M.
AU - Mahadevan, D.
N1 - Funding Information:
We wish to acknowledge the P30 supplement of NCI 2P30CA023074 grant to the University of Arizona Cancer Center..
Funding Information:
This work was supported by the NCI 2P30CA023074 grant to the University of Arizona Cancer Center.
Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Introduction: Prognosis remains dismal for pancreatic ductal adenocarcinoma (PDAC). Genomics and proteomics have depicted heterogeneity in PDAC. Collectively, this information could be useful in improving diagnosis, prognosis, modalities of therapy, treatment responses, deciphering drug resistance and new drug development. Areas covered: We describe major advances in the cellular and molecular subtypes based on next-generation sequencing and their predictive and prognostic value in PDAC patients. We review aberrant genes involving in defined cellular processes in PDAC. Finally, the current state of drug development with novel investigational agents targeting cell fate, cell survival, genomic instability, tumor-stroma, and immune checkpoints are discussed. Expert opinion: Molecular techniques have revealed distinct driver mutations in PDAC. Common genes and cellular processes are dysregulated in the pathogenesis of PDAC. These cellular processes categorized by aberrant pathways include control cell fate, genome maintenance, and cell survival. Dysregulation of the tumor microenvironment promotes an intense fibrosis and immune suppression that play a major role in drug resistance. New information on tumor biology has led to the development of targeted/stromal therapies, immunotherapies or combinations with current chemotherapy in PDAC. New drug development targeting multiple hallmarks of PDAC we hope will positively impact the quality and survival of PDAC patients.
AB - Introduction: Prognosis remains dismal for pancreatic ductal adenocarcinoma (PDAC). Genomics and proteomics have depicted heterogeneity in PDAC. Collectively, this information could be useful in improving diagnosis, prognosis, modalities of therapy, treatment responses, deciphering drug resistance and new drug development. Areas covered: We describe major advances in the cellular and molecular subtypes based on next-generation sequencing and their predictive and prognostic value in PDAC patients. We review aberrant genes involving in defined cellular processes in PDAC. Finally, the current state of drug development with novel investigational agents targeting cell fate, cell survival, genomic instability, tumor-stroma, and immune checkpoints are discussed. Expert opinion: Molecular techniques have revealed distinct driver mutations in PDAC. Common genes and cellular processes are dysregulated in the pathogenesis of PDAC. These cellular processes categorized by aberrant pathways include control cell fate, genome maintenance, and cell survival. Dysregulation of the tumor microenvironment promotes an intense fibrosis and immune suppression that play a major role in drug resistance. New information on tumor biology has led to the development of targeted/stromal therapies, immunotherapies or combinations with current chemotherapy in PDAC. New drug development targeting multiple hallmarks of PDAC we hope will positively impact the quality and survival of PDAC patients.
KW - Pancreatic ductal adenocarcinoma
KW - driver mutations
KW - immunotherapy
KW - molecular subtypes
KW - precision medicine
KW - targeted therapy
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U2 - 10.1080/13543784.2019.1557145
DO - 10.1080/13543784.2019.1557145
M3 - Review article
C2 - 30539678
AN - SCOPUS:85060176807
SN - 1354-3784
VL - 28
SP - 161
EP - 177
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 2
ER -