The additive effect of CTLA-4 knockdown together with Docetaxel treatment significantly downregulated BCL-2 level and upregulated BAX expression. Our findings support the idea that combining chemotherapy such as Docetaxel with efficient targeted therapy against inhibitory immune checkpoints can be a promising strategy in cancer treatment.

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

Our ER stress model performed a valuable prediction on breast cancer patients.

circUBR5 knockdown facilitated miR-340-5p-targeted CMTM6 via a ceRNA mechanism, thereby reducing c-MYC-mediated ribosome biogenesis and accelerating chemosensitization of DTX-resistant TNBC cells, which offered a theoretical guideline for clinical research on the feasibility of inhibiting ribosome biogenesis to reduce TNBC chemoresistance.

P1/2, N=48, Active, not recruiting, Zhuhai Beihai Biotech Co., Ltd

The patient was diagnosed as having stage IV HER2-positive breast cancer, which was treated with a regimen of trastuzumab (8 mg/kg), pertuzumab (first dose: 840 mg; second dose onward: 420 mg) and docetaxel (75 mg/m2) every 3 weeks. After 4 months of chemotherapy, the patient received complete remission. In conclusion, concomitant use of rifampicin and clarithromycin may increase the blood concentration of docetaxel.

This study uncovers a paracrine mechanism of chemoresistance in PCa and proposes that targeting the stroma could be a therapeutic choice.

DYRK2 plays a pivotal role in overcoming docetaxel resistance in breast cancer cells by suppressing Twist1 expression through ubiquitination, impacting downstream signaling and cellular responses. This study provides valuable insights for developing targeted therapies to improve breast cancer treatment outcomes.

This study reports, for the first time, mechanistic findings through which the combination of CXCR1/2 inhibition and docetaxel chemotherapy exhibits synergy in models of HPV-negative HNSCC. These findings provide rationale for the use of this novel combination approach to treat HPV-negative HNSCC patients and for future combination studies of CXCR1/2 inhibition, docetaxel, and immune-based therapies.

P=N/A, N=192, Active, not recruiting, University College, London | Recruiting --> Active, not recruiting | Trial completion date: Mar 2030 --> Oct 2030 | Trial primary completion date: Apr 2024 --> Nov 2024

The resistance of MM stem-like cells to ATRA can be attenuated by RES and combined applications of ATRA and RES provide a promising strategy for MM treatment.

Based on the consensus observed, the steering group developed a set of recommendations for the clinical utility of ADT+DOCE+ARTA in treating patients with mHSPC in the UK. Following these recommendations enables clinicians to identify appropriate patients with mHSPC for triplet treatment, thereby improving patients' outcomes.

PAF1 depletion was also associated with decreased pluripotent TFs and other CSC markers. This study provides a novel regulatory mechanism of docetaxel resistance in PCa through PAF1 and establishes clinically relevant docetaxel-resistant PCa cell lines.

P2, N=190, Recruiting, Yale University | Trial completion date: Oct 2024 --> Mar 2027 | Trial primary completion date: Oct 2024 --> Mar 2027

Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. These markers were also present in a subset of patient CTCs and are associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and the expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.

P3, N=126, Terminated, Sunshine Coast Cancer Centre, Nambour General Hospital | Not yet recruiting --> Terminated

P2, N=6, Terminated, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | was significantly higher than anticipated. Decision made to close due to insufficient patient numbers to able to obtain meaningful data collection.

The knockdown of circRNF19A was observed to notably inhibit the proliferation, invasion, migration and docetaxel resistance of PCa cells...Finally, the androgen receptor (AR) was observed to bind to the promoter region of the RNF19A gene, subsequently regulating the expression of circRNF19A and circRNF19A-490aa. These data indicate that circRNF19A plays a pivotal role in AR activation and AR-V7 generation by encoding a novel protein, circRNF19A-490aa, and targeting circRNF19A may prove an effective strategy for impeding the progression of CRPC.

Compared with the low-risk group, patients in the high-risk group demonstrated increased sensitivity to cisplatin, docetaxel, and paclitaxel. Furthermore, IGF2BP2, a potential target gene of MAFG-DT, was found to be overexpressed in tumor tissues and correlated with overall survival (OS). Our study demonstrated that the predictive signature based on eight redox-related lncRNAs can independently and accurately predict the prognosis of BCa patients.

IRAK2 also influenced the sensitivity of prostate cancer cells to docetaxel (DTX), and silencing IRAK2 reversed the anti-tumor effects of DTX on prostate cancer cells. Our findings suggest that IRAK2 functions as a tumor suppressor in prostate cancer and may serve as a potential therapeutic target for developing effective treatments for prostate cancer.

Our investigation of TACC3 revealed its potential as a promising target both for immunosuppression and docetaxel resistance in pan-cancer, especially in lung adenocarcinoma.

sTK1 was examined in three cohorts: (1) 43 men with de novo mHSPC managed with androgen deprivation monotherapy; (2) 99 patients with mCRPC managed with androgen receptor signaling inhibitors (ARSIs); and (3) 98 patients with mCRPC treated with docetaxel...We found that for patients with metastatic prostate cancer, high levels of a protein called TK1 that is involved in cell division was linked to higher risk of death. Our findings need to be confirmed in other studies.

P3, N=630, Recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Enrolling by invitation --> Recruiting

P2, N=34, Recruiting, University of Florida | Not yet recruiting --> Recruiting

Additionally, heightened sensitivity to paclitaxel and docetaxel was evident in the patients at high risk. We have established a BMLncRNA-based prognostic model that can provide clinical guidance for future laboratory and clinical studies of HNSCC.

This is the first randomised phase 3 trial in the setting of PDT in patients with oligoprogressive mCRPC with OS as the primary endpoint.

We previously developed and validated a signature reflecting low TSG expression (TSGlow) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel...We found that patients with low expression of two out of three tumor suppressor genes (TP53, RB1, PTEN) had worse clinical outcomes and had aggressive variants of prostate cancer. Measuring the expression of these genes in early-stage prostate cancer could help in finding better treatments for these patients.

Depletion of USP3 or SMARCA5 promoted PCa cells sensitive to docetaxel and overexpression of USP3 restored the cells resistance to docetaxel treatment in SMARCA5 silenced cells in vitro and vivo. Clinically, USP3 was significantly up-regulated in prostate cancer tissues and positively associated with SMARCA5 expression. Collectively, our findings uncover a novel molecular mechanism for the USP3-SMARCA5 axis in regulating DSB repair with an important role in chemotherapy response in human prostate cancers, highlighting that targeting USP3-SMARCA5 axis could be a valuable strategy to treat USP3/SMARCA5-overexpressing chemotherapy-resistant patients and improve drug treatment.

Moreover, MPD3 elicited robust anti-tumor activities in both local and liver metastatic PDAC tumor models in mice. Overall, this work establishes a paradigm for developing translational pan-KRAS cancer treatment and broadens the applicability of albumin binding peptide-drug conjugate against albumin-metabolism enriched cancers.

These findings highlight IRX4_PEP1 role in PCa stemness and chemoresistance, suggesting it as a therapeutic target and potential diagnostic marker.

Treatment regimens in the T-AC group included anthracycline + cyclophosphamide (dose dense or standard) followed by taxane (n = 298, 68%), concurrent anthracycline, cyclophosphamide, and docetaxel (n = 59, 14%), and other anthracycline + taxane combinations (n = 80, 18%). Patients with early-stage, HR+/HER2-negative breast cancer and high RS values (> 31) may benefit from adjuvant taxane and anthracycline-containing therapy more than from TC. Genomic RS testing may predict anthracycline benefit more accurately than other factors such as nodal status.

Before Oncotype DX results, clinician recommended CT for 60.1% of pts, with docetaxel-cyclophosphamide (59.1%) as the preferred chemotherapy regimen. Without Oncotype DX results, the agreement in treatment recommendations between GTP-4o and clinicians was modest, and this discordancy deserve deeper investigation. Pre-test indications provided by GPT-4o were less impacted by the multigene assay results, maybe due to the capability of AI to better approximate Oncotype DX results. After Oncotype DX results, the agreement between AI and clinicians was extremely high indicating the key role of multigene testing in guiding treatment decisions.

Anthracycline and Taxane-based regimens were most common (76%), followed by Docetaxel and Cyclophosphamide (24%). This study presents the first real-world data on the implementation of Prosigna® in the UK, potentially optimizing future national guidelines. These findings highlight the importance of tumor grade and prognostic indices in risk stratification, offering valuable insights for personalized breast cancer management.

Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. These markers were also present in a subset of patient CTCs and associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and their expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.

The DTX-embedded and peptide-modified nanoparticles mitigated the side effects of DTX, enhanced cytotoxicity in TNBC MDA-MB-231 cells, and exhibited remarkable antitumor efficacy and safety in TNBC-bearing mice with HuR CRISPR deletion. Collectively, the combination therapy of DTX and CRISPR/Cas9 offers an effective platform for delivering antineoplastic agents and gene-editing systems to combat tumor resistance and progression in TNBC.

Our study revealed that the combination of CAPE with docetaxel is more effective at reducing the proliferation and survival of NSCLC cells, and this is via inhibition of c-MYC. Combined therapy of docetaxel and CAPE may benefit patients with NSCLC.

P2, N=70, Recruiting, Trigone Pharma Ltd.

P1, N=27, Suspended, Wake Forest University Health Sciences | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

Pembrolizumab is approved for solid tumors with a high tumor mutation burden (TMB) and/or high microsatellite instability, and nivolumab was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies. Even in the cases with a high TMB, the response to anti-PD-1 therapy was not sufficient. Most cases involve second-line or later treatments, so further research is needed to determine the precise effectiveness of anti-PD-1 therapy as a first-line treatment.

In conclusion, anthracycline followed by docetaxel improved outcome compared with DC in patients with TOP2A normal early breast cancer, and no clinical value of TOP2A testing was shown. The risk of HF was doubled in patients receiving anthracycline; however, overall, the risk of HF was low.

P3, N=276, Completed, NovoCure GmbH | Active, not recruiting --> Completed

NPs treated groups demonstrated notable tumor growth inhibition in 4T1 tumor bearing Balb/c mice by only 1/10th of the DTX therapeutic dose (TD) as a drug model. In conclusion, cleverly designed nanostructures here demonstrated improved anticancer effects by enhancing tumor targeting, delivering chemotherapeutic agents more accurately, promoting drug release, reducing the therapeutic dosage, and lowering side effects of anticancer drugs.