ORC1 (Origin Recognition Complex Subunit 1)

Molecular docking identified a high-affinity interaction between sorafenib and KIF20A (binding energy: -6.11 kcal/mol), suggesting direct targeting. The current study unveiled KIF20A as a dual regulator of tumor-intrinsic malignancy and immune evasion, positioning sorafenib as a promising therapeutic agent to disrupt KIF20A-driven pathways in gastric adenocarcinoma.

Since loss of the tumor suppressor APC is common in TNBC, we investigated how APC depletion alters transcriptional adaptation to chemotherapy using RNA-seq profiling of MDA-MB-157 cells and APC knockdown derivatives under control, cisplatin, and paclitaxel treatment. Machine-learning feature selection (Random Forest + PLS-DA) identified a 43-gene discriminant signature enriched for regulators of cell cycle and DNA repair (CCNB3, ORC1, E2F2, UNG), cytokine signaling (CXCL2, IL11), and metabolic support. These findings suggest that APC loss primes TNBC cells for chemotherapy persistence through an energetically reinforced, transcriptionally flexible survival program, highlighting DDR-OXPHOS-translation and inflammatory circuits as potential therapeutic vulnerabilities.

ORC1 represents a promising therapeutic target, as its inhibition induces replication stress, cell cycle arrest, and enhances sensitivity to existing chemotherapeutic agents. Future research should focus on developing specific ORC1 inhibitors and exploring their synergistic potential with immunotherapy and targeted therapies.

Serum ORC1, driven by HBV integration, is a promising biomarker especially for AFP-negative HBV-HCC. Its combination with ESPL1 and AFP significantly improves early detection.

ORC6 represents a highly promising novel target for precision therapy in glioma. Potential approaches to target this pathway include disrupting the ORC6-replication axis using existing drugs (such as palbociclib) or natural products (such as baicalin).

It may serve as a potential biomarker for diagnosis, patient stratification, and guiding personalized therapy. Further research could enhance SOC management.

IGF2BP1 enhanced ORC1 expression by modulating its m6A methylation modification, significantly influencing NSCLC progression. This study underscored the importance of the IGF2BP1/ORC1 axis in cancer progression.

miR‑885‑5p overexpression sensitized liver cancer cells to the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib. The present findings collectively demonstrated that miR‑885‑5p induces cell cycle arrest and enhances CDK4/6 inhibitor sensitivity in liver cancer, suggesting its potential as a therapeutic target.

Our findings indicate that the risk model associated with mitochondrial metabolism may serve as a dependable prognostic indicator, facilitating tailored therapeutic strategies for CRC patients. TMEM86B promotes colorectal cancer progression, and its downregulation inhibits tumor growth in vitro and in vivo.

Following release from proteasome inhibition, cells with elevated levels of chromatin-bound Orc6 and MCM proceed to the next replication phase as tetraploid cells. Our findings suggest that the proteasome-dependent dissociation of Orc6 after DNA replication is critical for preventing inappropriate MCM reloading and tetraploid formation.

Due to its binding at the origin-promoter locus like the MCM4 gene, ETV4 overexpression increases R-loop formation, DNA damage, and cell death under external replication stress induced by topoisomerase I (TOP1) inhibitor. These findings highlight the dual role of ETV4 in replication and transcription and suggest that targeting TOP1 could be a synthetic-lethal approach in ETV4-overexpressed lung cancer.

Despite the lack of ORC, excess MCM2-7 is still loaded at comparable rates in G1 phase to license dormant origins and is also repeatedly loaded in the same S phase to permit re-replication. Thus, origin specification and excess MCM2-7 loading on origins do not require the six-subunit ORC in human cancer cell lines.