doxorubicin hydrochloride

P=N/A, N=31, Terminated, Albert Einstein College of Medicine | N=132 --> 31 | Active, not recruiting --> Terminated; Interventional component of study terminated prior to full enrollment

This study highlights the importance of OTULIN in OS chemoresistance and provides a promising approach for targeting the OTULIN-GPX4 axis to improve the prognosis of OS patients. Our findings offer new insights into the molecular mechanisms underlying OS chemoresistance and suggest potential therapeutic targets for future clinical interventions.

A 46-year-old woman with a diagnosis of triple-negative breast cancer(cT2cN3cM0, cStage ⅢC)received neoadjuvant chemotherapy with dose-dense doxorubicin and cyclophosphamide, followed by weekly paclitaxel...Therefore, the patient was treated with olaparib followed by chemotherapy but died 15 months after surgery because of treatment inefficacy...Additionally, in the KEYNOTE-522 study, the hazard ratio for the pembrolizumab group compared to the placebo group was 0.73 in the event-free survival analysis of patients with pCR. Therefore, it is recommended that patients receive chemotherapy in combination with pembrolizumab.

We demonstrated for the first time that Dgkζ augments p53 ubiquitin-proteasome degradation and ameliorates doxorubicin-induced cardiotoxicity by interacting with Hsp70 and E3 ligases such as E6ap and C-terminus of Hsp70-interacting protein.

Co-treatment of doxorubicin with ZnPcS4-PDT or TMPyP-PDT or a combination of both resulted in a decrease in the expression of EGFR and its downstream oncogenes NRAS, NF-κB, mTERT, and c-Myc, and an increase in the expression of the caspase-3 apoptotic gene. These results validate the therapeutic potential of combining doxorubicin with photodynamic therapy, highlighting the potential of this co-treatment strategy as a promising alternative for enhancing existing anticancer approaches.

In conclusion, Doxorubicin was observed to induce EMT6 apoptosis through the inhibition of SIRT2 and RelA proteins. The outcomes of both experimental and bioinformatic studies provide a novel perspective on the biological effects of doxorubicin and underscore the potential of inhibiting the SIRT2-RelA axis as a promising biological target for cancer therapy.

Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX)...Furthermore, when combined with aPD-1, NL/PLDs demonstrated strong antitumor effects and increased immunotherapeutic efficacy. This regulatory strategy provides new insights for enhancing immunotherapy by regulating tumor immunosuppressive signals and shows significant potential for clinical tumor treatment.

WBP2 upregulation-initiated the chemoresistance to doxorubicin was reversed by exogenous ITCH, which was not affected by ITCH C830A mutant. In in vivo model, exogenous ITCH obstructed WBP2-mediated chemoresistance, which was destroyed by the proteasome inhibitor (MG132)...Our findings present how ITCH/WBP2 signaling functions to link the intricate AMOTL2/c-JUN signaling networks in chemoresistant BC cells. Targeting WBP2 combined with c-JUN inhibitors may be a potential option to overcome chemoresistance in breast cancer patients.

In conclusion, this study proposes that eEF2K alleviates DIC by inhibiting GSK3β and improving autophagy dysfunction. eEF2K is a promising therapeutic target against DIC.

Moreover, silymarin treatment improved mitochondrial biogenesis through activation Nrf2/HO-1 axis. Collectively, silymarin nanoemulsion, at a 200-fold lower dose, can offer an innovative solution for cancer patients globally.

Inhibiting TRIM9 caused a decrease in the IC50 of doxorubicin (DOX), and significant increases in the intracellular uptake, retention and absorption of DOX in HepG2/ADR cells. These findings may provide new insights into the mechanism of MDR development. The MDR-related hub genes, especially TRIM9 may be targeted therapeutically to enhance the prognosis of patients with drug-resistant HCC.

Importantly, KH-3 sensitized TNBC cells to doxorubicin-induced apoptosis. In summary, this study delineates cFLIP's role in mediating doxorubicin resistance and identifies HuR as a positive regulator of cFLIP, offering a novel therapeutic avenue against chemoresistance in TNBC by combining HuR inhibition with doxorubicin.

DIOS-CoQ10 combination treatment showed significant improvement in histopathology of liver and kidney along with morphometry compared to DOX group. In conclusion, combining DIOS and CoQ10 exhibited synergistic protective activity against DOX-induced hepatic and renal insult via their antioxidant and anti-inflammatory properties.

P2, N=20, Recruiting, Fudan University

P3, N=1656, Not yet recruiting, Children's Oncology Group | Initiation date: Dec 2024 --> Mar 2025

P2, N=147, Active, not recruiting, Jules Bordet Institute | Trial primary completion date: Sep 2024 --> May 2025

P2, N=125, Not yet recruiting, University of Washington

The dog completed multiple weeks of traditional cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-based treatment and had a survival time of 43 days before the owner elected humane euthanasia. To our knowledge, this report represents a case of acute leukemia in a dog treated with leukoreduction before starting chemotherapy.

Prompt initiation of brentuximab-cyclophosphamide, doxorubicin, and prednisolone therapy ensued. This case underscores the rarity of MPE as an initial presentation of BIA-ALCL and highlights the significance of early recognition and consideration of rare lymphomas in patients with breast implants. Recognize the importance of considering breast implant-associated anaplastic large cell lymphoma in the differential diagnoses of malignant pericardial effusion.

An increase was observed in the TNF-α expression with 5-fluorouracil and doxorubicin compared to the control, while a notable decrease was recorded in the applications with vitamin c and curcumin (p < 0.05). This study demonstrates that vitamin c and curcumin exhibit a synergistic effect with chemotherapeutic agents in the inflammatory system.

Herein, we developed a vitamin D3-inserted lipid hybrid neutrophil membrane biomimetic multimodal nanoplatform (designated as NED@MnO2-DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO2) which were coated with a vitamin D3-inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO2-DOX exhibited great power to activate and amplify immune responses related to the cGAS STING pathway, bolstering the secretion of type I interferon-β and proinflammatory cytokines, promoting the maturation of DC cells and infiltration of CD8+T cells into the glioma tissue, thereby reversing the immunosuppressive microenvironment of glioma from a "cold" tumor to a "hot" tumor. The biomimetic multimodal nanoplatform has potential as a multimodal strategy for glioma-targeted treatment, especially holding considerable promise for the development of innate immune therapy for glioma.

The TLR2 pathway plays a crucial role in the sequestration of NVs by Mφs. A novel antiphagocytic strategy in which pretreatment of mice with SpB inhibits the clearance of NVs and prolongs their half-life in vivo, thereby improving delivery efficiency, was identified.

P2, N=36, Recruiting, Yale University | Not yet recruiting --> Recruiting

P2, N=30, Not yet recruiting, Sun Yat-sen University

Furthermore, MYSM1 exacerbated DOX-induced cardiotoxicity by enhancing ferroptosis. This study identified MYSM1 as a potential therapeutic target for DOX-induced cardiotoxicity and illustrated a MYSM1-TRIM21-ferroptosis axis in regulating DOX-induced cardiotoxicity.

The recognition and binding of the modified SLC50A1 by IGF2BP2 subsequently promote its stability and translational expression. Consequently, our research identifies the METTL3/SLC50A1 axis as a novel therapeutic target in the context of HCC.

In vitro, NAPs achieved a 73.9% doxorubicin (DOX) uptake in leukemic cells, compared to 6.19% for the free drug, while significantly reducing off-target accumulation in normal cells from 42.9% to 5.76%...NAPs demonstrated antileukemic activity in both in vitro and in vivo NSG mouse models, inducing cell death via apoptosis and ferroptosis. In conclusion, NAP-mediated targeted drug delivery represents a promising therapeutic strategy for AML, enhancing treatment efficacy and minimizing off-target effects.

Chemotherapy includes the use of doxorubicin or taxanes generally with platinum-based drugs viz. cisplatin or carboplatin that are administered alone or along with multitarget tyrosine kinase inhibitors viz. Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Pyrazolo-pyrimidine compounds, etc., single target tyrosine kinase inhibitors like Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, Everolimus against mTOR, vascular disruptors like Fosbretabulin, and immunotherapy with viz. Spartalizumab and Pembrolizumab, are anti-PD-1/PD-L1 molecules...Hence, our review presents a closer view of NDDS as a personalized treatment for TC. We have also discussed the primary challenges facing NDDS in meeting excellence in PM.

This was supported by increased reactive oxygen species production, upregulation of pro-apoptotic genes, downregulation of anti-apoptotic genes, and elevated caspase 3 and 7 activity, collectively promoting apoptosis. These findings underscore the potential of DOX-BSA-NPs as a superior alternative for targeted and controlled drug delivery, offering enhanced therapeutic efficacy and reduced side effects in ovarian cancer treatment.

P2, N=41, Active, not recruiting, Jennifer Crombie, MD | Recruiting --> Active, not recruiting

The reversal effect of the isoquinoline alkaloid coptisine (COP) was assessed on four breast cell lines; Two sensitive MCF-7 cell lines with positive estrogen, androgen, progesterone, and glucocorticoid receptors, as well as MDB-MB-231 cells with negative estrogen, progesterone, and HER2 receptors, and two doxorubicin-resistant cell lines, MCF-7/ADR and MDB-MB-231/ADR...The inhibitory effect of COP on ABCT efflux function in comparison to verapamil (VER) was evaluated by measuring the cellular accumulation of Rho123 using flow cytometry...The combination of COP and DOX had a strong inhibitory effect on ABCT function (3.1 and 3.9 times VER, P< 0.001) and downregulated the genes and protein expression of ABCT. COP reversed ABCT-mediated multidrug resistance in vitro, indicating its potential as a multidrug resistance-reversing agent in cancer chemotherapy.

CPE could increase renal function by reducing BUN and creatinine levels, increasing albumin, and improving the histopathology of the kidney. CPE has a potential effect as nephroprotective against doxorubicin-induced toxicity in renal through antioxidant capacities and increased renal function.

P1, N=158, Recruiting, Avacta Life Sciences Ltd | N=80 --> 158 | Trial completion date: Jun 2023 --> Aug 2026 | Trial primary completion date: May 2023 --> Mar 2026

P1/2, N=10, Not yet recruiting, Zhejiang Cancer Hospital

P2, N=30, Not yet recruiting, University of Washington

First, we formulated an injectable photothermal bioactive glass (BG)-based hydrogel for the local delivery of Siglec-15 shRNA and doxorubicin...The combined effect of BGs and Siglec15 shRNA can normalize dysregulated bone homeostasis at the bone metastasis site and significantly reduced bone destruction. Overall, the use of Siglec-15-targeting integrated BG hydrogels may provide a promising therapeutic strategy for treating bone metastasis caused by breast cancer.

One patient received adjuvant radiotherapy, whereas the other received ifosfamide and doxorubicin-based therapy. There was a suboptimal response to chemotherapy in both patients.This study highlights the clinicopathological features of two rare and emerging sarcomas. It further emphasizes the value of high-throughput molecular testing, such as next-generation sequencing in the undifferentiated epithelioid, and spindle-cell sarcomas to identify the prognostic subtypes and differentiate these neoplasms from their histopathological mimics.

The expression of chemoresistance genes has been detected, including KLF4 (doxorubicin and ifosfamide), ULK1, LUM, GPNMB, and CAVIN1 (doxorubicin), and AHNAK2 (gemcitabine) in tumor cells and ETS1 (gemcitabine) in TME. This study provides the first description of the single-cell transcriptome of UPS with resistance to two lines of chemotherapy, showcasing the gene expression in subpopulations of tumor cells and TME, which may be potential markers for personalized cancer therapy.

In the in vitro extract recorded, promising anticancer effects in A540 cell lines with IC50 were close to the reference drug, doxorubicin (14.3 and 13.8 μg/mL, respectively)...The histopathological examination revealed that Purslane extract showed markedly improved tissue structure and reduced pathological changes across all examined organs caused by NNK. The anti-lung cancer effect exhibited by the extract may be linked to the active ingredients of the extract that were characterized by LC-MS, such as α-linolenic acid, linoleic acid, palmitic acid, β-sitosterol, and alkaloids (berberine and magnoflorine).

Rats given SAE had promising levels of phytochemicals, which could significantly ameliorate DOX-induced hepatotoxicity by restoring biochemical alterations, mitigating ferroptosis, and upregulating the NRF-2-SLC7A-11-GPX-4 signaling pathway. These findings suggest that SAE could potentially alleviate DOX-induced hepatotoxicity in rats.

Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.

Treatment for the PNET included vincristine, doxorubicin, cyclophosphamide, and ifosfamide/etoposide mesna...The patient also underwent a tandem autologous stem cell transplant with carboplatin/etoposide conditioning and adjuvant etoposide and the subsequent PET/CT scan showed a response to the above treatment...The regimen for our patient yielded promising results. Our aim is to highlight a regimen that can be utilized for this rare aggressive neoplasm.