Aprepitant was orally administered every alternate day between days 2 and 14, with a prescribed dosage of 10 or 20 mg/kg. In addition, aprepitant application suppressed the protein expression of NF-kB in the dorsal root ganglia of paclitaxel-treated rats, as revealed by western blot analysis. Aprepitant treatment ameliorates neuropathy induced by paclitaxel, which is associated with decreasing proinflammatory cytokines and NF-kB expression.
In a similar manner, a low-dose taxol treatment rescued mitotic errors in a high-grade serous ovarian carcinoma cell line OVKATE. Collectively, our results highlight the potential of targeting microtubule poleward flux to modify chromosome instability and provide insight into the mechanism through which low doses of taxol rescue certain mitotic errors in cancer cells.
Herein, a "one stone and three birds" nanococktail integrated by a cocrystal@protein-anchoring strategy was purposed for triple-payload delivery, which paclitaxel-disulfiram cocrystal-like nanorods (NRs) were anchored with the basic protein drug Cytochrome c (Cyt C), followed by hyaluronic-acid modification. Our mechanistic study indicated that the system induced the apoptosis of Taxol-resistant tumor cells through the signal axis P-glycoprotein/Cyt C/caspase 3. Collectively, this nanococktail strategy offers a promising approach to improve the sensitivity of tumor cells to chemotherapeutic drugs and strengthen intractable drug-resistant oncotherapy.
Overall, this study underscores the effectiveness of multi-omics approaches in revealing the molecular mechanisms driving chemotherapy responses in cancer cells. Additionally, this work generates a comprehensive list of molecular alterations that can serve as a foundation for further investigations and inform personalized healthcare strategies to enhance patient outcomes.
2 days ago
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • RACK1 (Receptor For Activated C Kinase 1) • RPA3 (Replication Protein A3)
Our investigation of TACC3 revealed its potential as a promising target both for immunosuppression and docetaxel resistance in pan-cancer, especially in lung adenocarcinoma.
2 days ago
Journal • IO biomarker • Pan tumor
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TACC3 (Transforming acidic coiled-coil containing protein 3)
This result was superior to the second-line treatment with nab-paclitaxel, which resulted in a PFS of 8 months and best overall response of stable disease with slight shrinkage. The present case indicates that a combination of utidelone with apatinib/anlotinib exhibited antitumor activity in a patient with HR+/HER2- mBC with BMs. Therefore, this combination offers a promising therapeutic option for the clinical treatment of patients with breast cancer and BMs.
3 days ago
Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HR positive • HER-2 negative
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Focus V (anlotinib) • AiTan (rivoceranib) • albumin-bound paclitaxel • utidelone IV (UTD1)
Accordingly, the biologically derived nanovesicles from ginger (GDNVs) with excellent P. gingivalis elimination ability are explored to transport the clinically used drug paclitaxel (PTX) for potentiating the therapeutic efficiency...By evaluating both P. gingivalis-infected tumor cells and P. gingivalis-infiltrated tumor-bearing mice, P-GDNVs show a much enhanced tumor cell killing effect, as compared with free PTX. This naturally occurring nanotherapeutic system represents an effective bioactive material for targeted elimination of host microbiota to boost therapeutic response, showing great promise to combat commensal microbiota-rich tumors.
Germline pathogenic/likely pathogenic (P/LP) variants in BRCA2 and ATM genes are associated with a shorter time to progression and rarer P/LP variants in other DRG genes may play a role in mCRPC. This justifies the use of routine screening of men with advanced PrCa for germline variants and supports the need for an expanded panel test.
3 days ago
Journal • BRCA Biomarker • Metastases
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BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase)
As mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.
The antiproliferative activity of MH was determined using MTT and colony formation assays against drug-sensitive (A549 and H1299) and Taxol-resistant lung cancer cells (A549-TR)...In vivo, MH (25 mg/kg b. wt.) significantly (p < 0.001) inhibited the growth of A549 lung cancer orthotopic xenografts in NOD Scid mice by 70%. Our study provides new mechanistic insights into MH's therapeutic potential against NSCLC.
The patient was treated with a chemotherapy regimen of pemetrexed and carboplatin. Mesothelioma with predominantly intrapulmonary growth is extremely rare and poses a diagnostic pitfall. For this entity, subtle morphological features, selection of immunohistochemical markers, and electron microscopy are of great significance for definite diagnosis.
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.
3 days ago
Clinical • Journal • Metastases
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AURKB (Aurora Kinase B) • CDK7 (Cyclin Dependent Kinase 7)
P=N/A, N=304, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi
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.
P=N/A, N=30, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024 | Trial primary completion date: Mar 2025 --> Nov 2024
11 days ago
Trial completion • Trial completion date • Trial primary completion date
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.
12 days ago
Journal • Metastases
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
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.
12 days ago
Journal
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SMARCA5 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 5)
Rescue experiments confirmed the pivotal role of SIRT1 in USP49-mediated CBP resistance. Our findings delineate a novel molecular network involving USP49-mediated autophagy in promoting CBP resistance in RB, offering potential targets for therapeutic intervention to enhance treatment efficacy and improve outcomes for RB patients.
13 days ago
Journal
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SIRT1 (Sirtuin 1) • IGF2BP3 (Insulin Like Growth Factor 2 MRNA Binding Protein 3)
P2, N=14, Active, not recruiting, Barts & The London NHS Trust | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2025 | Trial primary completion date: Jun 2021 --> Jun 2025
13 days ago
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
Taken together, NM enhanced the CBP sensitivity of ovarian cancer cells by promoting the ZNF24-mediated inactivation of the WNT2B/Wnt/β-catenin axis. These findings suggest a viable treatment approach for improving CBP resistance in ovarian cancer.
GB1-7 showed excellent solubility and much higher than that of paclitaxel...Passive permeability was predicted to be high based on PAMPA. Parent compound GB1 (1a) was further evaluated using a cellular model with MDCK cells stably transduced with the human efflux transporter MDR1/P-gp, showing similar permeability with and against transporter gradient, indicating that GB1 (1a) is a poor P-gp substrate.
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.
P2, N=65, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025
14 days ago
Trial completion date • Trial primary completion date
The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study.
This study revealed the important significance of SM in PC and identified SM-associated molecular subtypes and prognostic model, which provided novel perspectives on the stratification, prognostic prediction, and precision treatment of PC patients.
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.
17 days ago
Journal
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TNFRSF9 (TNF Receptor Superfamily Member 9) • LRP1 (LDL Receptor Related Protein 1)
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.
To counteract monotherapy-induced tumor relapse, we assessed GSI-paclitaxel and dasatinib-paclitaxel combination treatments in NOTCH inhibitor-sensitive and -resistant TNBC xenotransplants, respectively. These distinct preventive combinations and second-line treatment option dependent on NOTCH1 and SOX2 expression in TNBC are able to induce tumor growth control and reduce metastatic burden.
Additionally, SIRT7-mediated crotonylation of MCM6 at K599 (MCM6-K599cr) was significantly upregulated in response to DNA replication stress, primarily due to the disassemebly of the MCM2-7 complex and regulated by RNF8-mediated ubiquitination. Concurrently, kaempferol, which acts as a regulator of SIRT7, was found to enhance the Kcr level of MCM6, reducing tumour weight, particular when combined with paclitaxel, highlighting its potential chemotherapeutic target for BRCA therapy.
18 days ago
Journal
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BRCA (Breast cancer early onset) • MCM2 (Minichromosome maintenance complex component 2) • RNF8 (Ring Finger Protein 8) • SIRT7 (Sirtuin 7) • MCM6 (Minichromosome Maintenance Complex Component 6)
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.