Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance

Rana Muhammad Usman, Faryal Razzaq, Arshia Akbar, Arafat Ali Farooqui, Ahmad Iftikhar, Azka Latif, Hamza Hassan, Jianjun Zhao, Jennifer S. Carew, Steffan T. Nawrocki, Faiz Anwer

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)193-208
Number of pages16
JournalAsia-Pacific Journal of Clinical Oncology
Volume17
Issue number3
DOIs
StatePublished - Jun 2021

Keywords

  • Autophagy-related genes
  • autophagy
  • drug resistance
  • hydroxychloroquine
  • tumorigenesis

ASJC Scopus subject areas

  • Oncology

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