ERCC1 expression

Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination...Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed.

Furthermore, the downregulation of ERCC1 expression by siRNA ameliorates drug resistance to cisplatin (DDP) chemotherapy...The results of the present study highlighted the critical effect of oncolytic virus Ad‑siERCC1 in inhibiting the survival of ovarian cancer cells and increasing chemotherapy sensitivity to DDP. These findings underscore the potent antitumor effect of Ad‑siERCC1 on ovarian cancers in vivo.

Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

P2, N=120, Recruiting, Christopher Wilke | Unknown status --> Recruiting | Trial completion date: Dec 2021 --> Dec 2030 | Trial primary completion date: Dec 2020 --> Dec 2030

This analysis reinforces KRAS mutations as predictive factors for relapse and poor survival in localized non-sq NSCLC. Furthermore, the presence of concomitant STK11/LKB1 mutations exacerbated the prognosis within the KRAS-mutated subset. These findings emphasize the clinical relevance of these molecular markers and their potential impact on treatment strategies in non-sq NSCLC.

P1/2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024

Of these, 22 compounds emerged as promising enhancers of cisplatin efficacy. Our results underscore the value of pinpointing crucial molecular characteristics in the pursuit of novel modulators of the ERCC1-XPF interaction, which could be combined with cisplatin to treat NSCLC more effectively.

P1/2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

In AGS gastric cancer cells, a 64% decrease was detected for GST levels in compound 1, while a 38% decrease in GSH levels in compound 2. In addition, compounds 1-3 were examined at the molecular level with computational techniques and the docking studies revealed 4LN0 as a target protein.

Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.

Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer.

The results showed that low level of Se and high levels of V, As, Sn, Ba, Pb, Cr, and Cu increased the risk of CRC. Sb and Tl may cause BRAF V600E mutations, leading to MSI. XRCC1 (rs25487) was positively correlated with Se but negatively correlated with Co. The expression of ERCC1 may be related to MSS, while the XRCC1 (rs25487) polymorphism is related to MSI.

These findings show that XPF-ERCC1 blockers not only increase the toxicity of chemotherapy drugs but also increase the efficacy of combined chemoradiotherapy. In the future, the XPF-ERCC1 blocker may be used to improve the efficacy of 5-FU- and oxaliplatin-based CRT.

P=N/A, N=52, Not yet recruiting, Assiut University

We showed that detection of HPV in CTCs from patients with non-metastatic SCCA is feasible and appears to be a sensitive diagnostic method. These results may be clinically useful for better monitoring these patients. However, future larger cohorts may demonstrate whether there is any correlation between the presence of HPV and the expression of screening markers for CRT in SCCA.

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023

Experimental studies indicated that the biological effects exerted by ERCC1 in cervical cancer might be mediated by its associated genes and affected signaling pathways (i.e., XPF, TUBB3, and. To move towards clinical applications by targeting ERCC1 in cervical cancer, more clinical, in-vitro, and in-vivo investigations are still warranted in the future.

Decreased TS protein expression can be indicative of greater responsivness to pemtrexed and of longer TTP and OS in individuals with advanced MPM (locally progressed or metastatic) who are receiving pemetrexed-based chemotheraphy. Low ERCC1 expressions in individuals with advanced MPM can predict increased PFS and OS, as well as a better responsivness to platinum-based chemotherapy. In patients with progressed MPM receiving gemcitabine plus cisplatin chemotherapy, lower RRM1 expression was associated with a better prognosis, longer PFS, and longer OS.

All patients received concurrent chemoradiotherapy (total dose of 70 Gray in 35 fractions in 7 weeks with concurrent tablet capecitabine 1250 mg/m/day)...Posttreatment expression levels of CYP2A6 were found to be a better predictor for tumor response to the treatment than the pretreatment expression levels. Almost all the patients having higher RQ folds had CR and those having lower RQ folds had either no response or progressive disease on follow-up visits.

After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo...The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.

Mechanistically, we performed tumour chemosensitivity assay to observe the convincing linkage of rs3212986 polymorphism with ERCC1 expression and cisplatin sensitivity...It reminded that patients carrying ERCC1 rs3212986 CC homozygote were expected to respond better to platinum-based chemotherapy due to a lower expression of ERCC1. Compared with previous studies, our current comprehensive study suggested that rs3212986, a 3'UTR polymorphism in ERCC1, might have clinical relevance in predicting the prognosis of NSCLC patients receiving platinum-based chemotherapy.

To investigate the relationship between Excision repair cross-complementation 1 (ERCC1) expression, clinicopathological features, and breast cancer prognosis in patients treated with trastuzumab...A correlation was observed between high ERCC1 expression and poor patient prognosis. High ERCC1 expression also influences the efficacy of immunotherapy and chemotherapy.

Previous reports indicate that high levels of ERCC1 reduce the effectiveness of cisplatin-based CCRT; however, it remains unclear as to whether ERCC1 overexpression increases radiation resistance...For further verification, we exposed HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models to radiation and observed that ERCC1 overexpression increased colorectal cancer tumor radioresistance in both. Combined, our results suggest that ERCC1 overexpression may serve as a suitable CCRT prognostic marker for colorectal cancer patients.

mt KRAS NSCLC patients might benefit from a treatment strategy that targets KRAS in combination with therapeutic agents based on pharmacogenomic markers, such as SRC and BRCA1. mtKRAS tumors are likely to be platinum-, taxane-, and pemetrexed-resistant, as well as having a low level of PD-L1 expression; thus, they are less likely to receive single-agent immunotherapy, such as pembrolizumab, as the first-line therapy. wt KRAS tumors with BRCA1 positivity tend to be sensitive to taxane therapy and, potentially, platinum. Our results suggest the need to develop targeted therapies for KRAS-mutant NSCLC or combine the targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor.

Our findings also suggest that paroxetine is a promising candidate anticancer agent and/or chemosensitizing agent for use in combination with other anticancer drugs in cancer therapy. The molecular mechanisms underlying the anticancer activity of co-treatment with paroxetine and chemotherapy appear to be complex and are worthy of further investigation.

Subsequently, two experimental groups were treated with cisplatin in normothermia (Group 1) and hyperthermia (Group 2) (37˙C and 41˙C, respectively) while the control group was treated with phosphate-buffered saline solution 1X at 37˙C (Group 3) and 41˙C (Group 4) for 24 hours. The use of everolimus in HIPEC in vitro model increases the cytotoxic response and suggest that inhibition of the mTOR pathway modulates the expression of heat shock genes e ERCC1 gene improving outcomes. Nevertheless, there is still a need for studies evaluating the effectiveness of everolimus in preclinical trials under hyperthermic conditions.

In the genomics era, treatment should be tailored to the individual patient. The present study showed that PALB2 and ERCC1 expressions, assessed in pre-NACT biopsies, were lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.

Patients received Gemcitabine & Cisplatinum for at least 3 cycles. Lower levels of gene expression of BRACA1, ERCC1& higher expression of CTR were the only factors which remained statistically significant in multivariate analysis by logistic regression (table 1) Conclusions : Molecular profile has a decisive role in identifying patients who will get benefit from preoperative NAC. Lower mRNA expression levels of the genes ERCC1 (=3.65), BRACA1 (=3.21) in addition to higher gene expression of CTR (>14.2) were predictors for good response to cisplatinum based NAC in MIBC.

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2022

Combinatorial regimens or neferine/isoliensinine treatments downregulated the cell survival protein expression (PI3K/pAkt/mTOR) and activated mitochondria-mediated apoptosis by upregulating Bax, cytochrome c, caspase-3, and PARP cleavage expression while downregulating the BCl-2 expression in CSCs. Our study confirms the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimens of neferine/isoliensinine with a low dose of cisplatin against CSCs.

These cell lines were cultured continuously with escalating concentrations of Bortezomib (Btz) during 12 months and showed a significant resistance to Bortezomib compared to their parental cell lines (mean IC50: Btz-resistant HMCLs =5.5nM vs parental HMCLs=2.5nM, p<0.05). Of interest, we demonstrated that Btz-resistant HMCLs are also significantly more resistant to Carfilzomib (Cfz) and Ixazomib (Ixa) PIs (mean IC50: Btz-resistant HMCLs =6nM for Cfz and =70nM for Ixa vs parental HMCLs=3nM, for Cfz, p<0.05 ; and =21nM for Ixa, p<0.05. No significant cross-resistance was observed with other therapeutic agents including melphalan, dexamethasone and IMIDs indicating that the observed drug resistance mechanisms are specifically related to PIs...Metabolomic analyzes are currently ongoing for functional validation. Altogether, drug-resistant cell lines represent an attractive preclinical model to test molecules targeting these pathways in order to identify new therapeutic strategies to overcome PI resistance in MM.

We did not confirm a prognostic value of ERCC1 in the multivariate regression analysis. ERCC1 expression does not influence the overall survival of patients with urothelial bladder carcinoma after radical cystectomy.

Identifying patients resistant to cisplatin treatment is expected to improve cisplatin-based chemotherapy for various types of cancers...It showed a clear staining pattern in clinical specimens of gastric cancers. Antibody 9D11 may thus be useful for estimating expression levels of ERCC1 in clinical specimens.