TY - JOUR
T1 - Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance
AU - Usman, Rana Muhammad
AU - Razzaq, Faryal
AU - Akbar, Arshia
AU - Farooqui, Arafat Ali
AU - Iftikhar, Ahmad
AU - Latif, Azka
AU - Hassan, Hamza
AU - Zhao, Jianjun
AU - Carew, Jennifer S.
AU - Nawrocki, Steffan T.
AU - Anwer, Faiz
N1 - Publisher Copyright:
© 2020 John Wiley & Sons Australia, Ltd
PY - 2021/6
Y1 - 2021/6
N2 - A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.
AB - A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.
KW - Autophagy-related genes
KW - autophagy
KW - drug resistance
KW - hydroxychloroquine
KW - tumorigenesis
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U2 - 10.1111/ajco.13449
DO - 10.1111/ajco.13449
M3 - Review article
C2 - 32970929
AN - SCOPUS:85091448460
SN - 1743-7555
VL - 17
SP - 193
EP - 208
JO - Asia-Pacific Journal of Clinical Oncology
JF - Asia-Pacific Journal of Clinical Oncology
IS - 3
ER -