Cancers, Vol. 12, Pages 333: The Unfolded Protein Response: A Novel Therapeutic Target in Acute Leukemias

Cancers, Vol. 12, Pages 333: The Unfolded Protein Response: A Novel Therapeutic Target in Acute Leukemias Cancers doi: 10.3390/cancers12020333 Authors: Alberto M. Martelli Francesca Paganelli Francesca Chiarini Camilla Evangelisti James A. McCubrey The unfolded protein response (UPR) is an evolutionarily conserved adaptive response triggered by the stress of the endoplasmic reticulum (ER) due, among other causes, to altered cell protein homeostasis (proteostasis). UPR is mediated by three main sensors, protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6α (ATF6α), and inositol-requiring enzyme-1α (IRE1α). Given that proteostasis is frequently disregulated in cancer, UPR is emerging as a critical signaling network in controlling the survival, selection, and adaptation of a variety of neoplasias, including breast cancer, prostate cancer, colorectal cancer, and glioblastoma. Indeed, cancer cells can escape from the apoptotic pathways elicited by ER stress by switching UPR into a prosurvival mechanism instead of cell death. Although most of the studies on UPR focused on solid tumors, this intricate network plays a critical role in hematological malignancies, and especially in multiple myeloma (MM), where treatment with proteasome inhibitors induce the accumulation of unfolded proteins that severely perturb proteostasis, thereby leading to ER stress, and, eventually, t...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research