Page 81 - TD-3-4

Tumor Discovery RNA-protein complexes deregulated in cancer

Table 6. (Continued)
Compound Target Application References
Reserpine Induce cell death through BAX Antiproliferative effects on MDA-MB-231 283
and MST-1 upregulation and
downregulation of Bcl2, LATS-1,
and YAP
pH-responsive hexapeptide (VEALYL) Swelling of lysosomes Chemotherapy of MDR-overexpressing tumors 284
Actinomycin D (ActD), etoposide, Inhibit paraspeckles Reduction in size 285
flavopiridol
AKT inhibitor TAS0612, Inhibits YB-1 phosphorylation Reverse resistance to tamoxifen in BC 287
everolimus
2,4-dihydroxy-5-pyrimidinyl Block YB-1 translocation to the YB-1 cannot induce target genes, blocking BC 287
imidothiocarbomate, nuclei growth
6-O-angeloylplenolin sesquiterpene
lactone
MG132 proteasome inhibitor Activates GCN2 for the Cells defective in UPR, B-cell lymphoma, leukemias; 288
hyperphosphorylation of hyper phosphorylated eIF2a increases bortezomib
eIF2-alpha anticancer activity through eradication of quiescent
cancer cells
ISRIB peptide Pulmonary veno-occlusive disease, Fragile X 289,290
syndrome, neurodegenerative diseases, diseases
involving SG formation
FYVE finger-containing Induce a MiT/TFE transcription Improve glucocerebrosidase function in Gaucher 291
phosphoinositide kinase) modulator plus factor promoting lysosomal gene patient-derived fibroblasts
an integrated stress response antagonist translation
Abbreviations: CLL: Chronic lymphocytic leukemia; PDAC: Pancreatic ductal adenocarcinoma; PML: Promyelocytic leukemia protein;
GBM: Glioblastoma multiforme.
Pancreatic cancer cells have been shown to be sensitive MTAR1 recruits IGF2BPs into condensates, promoting
to 1,6-hexanediol, an LLPS inhibitor that also modulates their interaction with PABP1 and enhancing the stability
kinase and phosphatase activities. Experimentally applied and translation of myc Mrna. Similarly, MNX1‐AS1,
241
to cell cultures, 1,6-hexanediol reduced pancreatic cancer which is upregulated in NSCLC, facilitates MYC-mediated
growth in an orthotopic BxPC-3 xenograft model using the transcriptional activation. MNX1‐AS1 induces IGF2BP1
BXPC‑3 human pancreatic adenocarcinoma cell line. This phase separation, thereby increasing its interaction with the
compound inhibits the stability of SGs and disrupts weak mRNAs E2F1 and myc, both of which encode oncogenic
intermolecular hydrophobic interactions, likely through transcription factors and promote NSCLC cell proliferation.
241
alterations in hydrogen bonding. Transcriptional studies Since the MYC signaling pathway is oncogenic, it can serve
revealed that 1,6-hexanediol downregulates myc expression as a key target for therapeutic strategies.
as well as other genes involved in key signaling pathways, The PML nuclear body, a BC formed through LLPS,
including cytokine-cytokine receptor interactions, Wnt is relevant in leukemias where mutations in PML render
signaling pathway, extracellular matrix-integrin/cadherin patients resistant to arsenic-targeted therapy. 281
receptor interactions, mitogen-activated protein kinase
(MAPK) signaling, and focal adhesion pathways. 277 The induction of LLPS by NUP98 fusion oncoproteins
(FOs) is implicated in leukemia. Nearly 30 NUP98-FOs
Therapeutic approaches aimed at modifying cancer have been identified, associated with 5% of pediatric
phenotypes (proliferation, invasiveness, and chemotherapy acute myeloid leukemia (pAML) cases and 50% of
unresponsiveness) are collectively referred to as chemotherapy-resistant pAML cases. Strategies to
281
condensate-modifying therapeutics (c-mods). The targets counteract the oncogenic activity of NUP98-FOs depend
of c-mods include the regulation of physical properties, on the specific fusion protein involved. These strategies may
macromolecular networks, composition, dynamics, and include targeting transcriptional and epigenetic machinery
functions of specific BCs. 280 (e.g., HDAC inhibitors), addressing alterations in
Several oncogenes are influenced by ncRNA regulation, cooperating partners, or disrupting signaling and cell cycle
making these ncRNAs potential targets for small molecules pathways. For instance, VTP50469 disrupts interactions
that inhibit their activity. For instance, the ncRNA between NUP98 fusion proteins and chromatin in

Volume 3 Issue 4 (2024) 22 doi: 10.36922/td.4657