The Intricate Interplay between Cell Cycle Regulators and Autophagy in Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Cell-Cycle Regulators Modulate Autophagy
2.1. Cyclin-Dependent Kinase Inhibitors and Autophagy
2.1.1. The CIP/KIP Family and Autophagy
2.1.2. The INK Family and Autophagy
2.2. Cyclin-Dependent Kinases and Autophagy
2.2.1. S/G2/M Phases CDKs in the Control of Autophagy
2.2.2. G1 Phase CDKs in the Control of Autophagy
2.2.3. Non-Canonical CDKs and Autophagy
2.2.4. CDKs and Mitophagy
2.3. E2F Transcription Factors and Autophagy
3. Autophagy Modulates Cell-Cycle Regulators
3.1. Autophagy and Cyclin-Dependent Kinase Inhibitors
3.2. Autophagy, Cyclin-Dependent Kinases and Cyclins
3.3. Mitophagy and Cell-Cycle Regulators
4. Therapeutic Interventions Combining Cell-Cycle and Autophagy Modulators
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACN-ACIN1 | Apoptotic chromatin condensation inducer 1 |
AML | acute myeloid leukemia |
AMPK | 5′-AMP-activated protein kinase |
ATG | Autophagy Related |
BAG3 | BCL2 associated athanogene 3 |
BECN1 | Beclin 1 |
BNIP3 | BCL2 adenovirus E1B 19-kDa protein-interacting protein 3 |
CDK | Cyclin-dependent kinase |
CEBPα | CCAAT enhancer binding brotein alpha, |
CKI | Cyclin-dependent kinase inhibitor |
CQ | Chloroquine |
DIRAS3 | Distinct subgroup of the ras family member 3 |
DNMT1 | DNA methyltransferase 1 |
DRAM | DNA damage regulated autophagy modulator 1 |
EGF | Epidermal growth factor |
EMT | Epithelial–mesenchymal transition |
EndoB1 | Endophilin B1 |
FLCN | Folliculin |
GABARAP | GABA type A receptor-associated protein |
GAPDH | Glyceraldehyde-3-phosphate dehydrogenase |
GBM | Glioblastoma multiforme |
HCQ | Hydroxychloroquine |
HSP | Heat shock protein |
IL | Interleukin |
LAMTOR | Late endosomal/lysosomal adaptor |
LKB1 | Liver kinase B1 |
MAPK | Mitogen-activated protein kinase |
MDM2 | Mouse double minute 2 |
MET | Mesenchymal-epithelial transition |
MMP | Matrix metallopeptidase |
mTOR | Mechanistic target of rapamycin kinase |
PDAC | pancreatic ductal adenocarcinoma |
PDH | Pyruvate dehydrogenase |
PDK | Pyruvate dehydrogenase kinase |
PIK3C3 | Phosphatidylinositol 3-kinase catalytic subunit type 3 |
PINK1 | PTEN induced kinase 1 |
PKM | Pyruvate kinase M1/2 |
RKIP-PEBP1 | Phosphatidylethanolamine binding brotein 1 |
TFEB | Transcription factor EB |
TFE3 | Transcription factor binding To IGHM enhancer 3 |
TGFβ | Tumor suppressor transforming growth factor-β |
ULK | Unc-51 Like autophagy activating Kinase |
UVRAG | UV radiation resistance associated gene |
VEGF | Vascular endothelial growth factor |
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Intervention | Cancer Type | Refs |
---|---|---|
| Breast cancer, solid tumors | [56] |
| Solid tumors | [120] |
| Pancreatic cancer | [121] |
| Brain cancer (glioblastoma multiforme) | [122] |
| t(8;21) Acute myeloid leukemia | [123] |
[124] | ||
| Estrogen receptor-positive, HER2-negative metastatic breast cancer | [125] |
Clinical Trial | Official Title | Condition | Intervention | Study Description | ClinicalTrials.gov Identifiers |
---|---|---|---|---|---|
PALAVY | A phase II trial of Avelumab or hydroxychloroquine with or without palbociclib to eliminate dormant breast cancer | Early-stage ER + breast cancer | HCQ, Avelumab, palbociclib | Randomized, open label phase II clinical trial that will assess the safety and early efficacy of hydroxychloroquine or Avelumab, with or without palbociclib, in early-stage ER+ breast cancer patients who are found to harbor disseminated tumor cells (DTCs) in the bone marrow after definitive surgery and standard adjuvant therapy. | NCT04841148 |
ABBY | A phase II pilot trial of abemaciclib or abemaciclib and hydroxychloroquine to target minimal residual disease in breast cancer patients | Invasive breast cancer | abemaciclib HCQ | Randomized, open label phase II clinical trial that is testing whether the use of hydroxychloroquine and abemaciclib can reduce the number or eliminate DTCs in bone marrow. | NCT04523857 |
Hydroxychloroquine, abemaciclib, and endocrine therapy in hormone receptor positive (HR+)/Her 2 negative breast cancer |
HR+/Her 2- advanced breast cancer, advanced solid tumors | Abemaciclib HCQ | Non-randomized, open label phase I clinical trial that assessed safety, tolerability, and efficacy of abemaciclib combined with the autophagy inhibitor hydroxychloroquine in advanced solid tumors and HR+/Her 2-advanced breast cancer | NCT04316169 | |
Phase I/II safety and efficacy study of autophagy inhibition with hydroxychloroquine to augment the antiproliferative and biological effects of pre-operative palbociclib plus letrozole for estrogen receptor-positive and HER2-negative breast cancer | HR+/HER2-bbreast cancer | HCQ, letrozole, palbociclib | Open label phase I/II clinical trial investigating the side effects and best dose of hydroxychloroquine when given together with palbociclib and letrozole before surgery in treating patients with estrogen receptor positive, HER2-negative breast cancer. | NCT03774472 |
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Ziegler, D.V.; Huber, K.; Fajas, L. The Intricate Interplay between Cell Cycle Regulators and Autophagy in Cancer. Cancers 2022, 14, 153. https://doi.org/10.3390/cancers14010153
Ziegler DV, Huber K, Fajas L. The Intricate Interplay between Cell Cycle Regulators and Autophagy in Cancer. Cancers. 2022; 14(1):153. https://doi.org/10.3390/cancers14010153
Chicago/Turabian StyleZiegler, Dorian V., Katharina Huber, and Lluis Fajas. 2022. "The Intricate Interplay between Cell Cycle Regulators and Autophagy in Cancer" Cancers 14, no. 1: 153. https://doi.org/10.3390/cancers14010153