- |||||||||| SLC1A4 is associated with metabolic reprogramming in triple-negative breast cancer (Section 14) - Mar 5, 2024 - Abstract #AACR2024AACR_9652;
Taken together, SLC1A4 is a potential oncogene that not only induces rapid proliferation, aggressive invasion, and migration through metabolic reprogramming but also contributes to increasing cancer stem cell capabilities. In addition, it shows the sensitive response to ADR when SLC1A4 is low or absent, so it can be used as a treatment strategy for TNBC.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
A microneedle array patch chemo-immunotherapy for cutaneous squamous cell carcinoma (Section 4) - Mar 5, 2024 - Abstract #AACR2024AACR_9451;
Taken together, our results suggest that MAP delivery of doxorubicin may be a promising approach to cSCC treatment. and that proinflammatory neutrophils are likely an important component of the early infiltrate that leads to tumor regression.
- |||||||||| ivospemin (SBP-101) / Panbela Therap
Ivospemin/doxorubicin combination modulates polyamine metabolism to improve survival in murine ovarian cancer models (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_9425;
Ivospemin treatment reduces cell viability in ovarian adenocarcinoma cell lines and increases the toxicity of doxorubicin regardless of cisplatin sensitivity...Recognizing the non-representative mutational status of the VDID8+ model as a limitation, we are currently evaluating the combination of ivospemin and doxorubicin in genetically defined murine models that better recapitulate human high-grade serous ovarian carcinomas. Ongoing studies will determine influences on the tumor microenvironment and will mechanistically evaluate the cooperativity of ivospemin and doxorubicin on pathways outside of polyamine metabolism.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Entresto protects against doxorubicin-induced cardiotoxicity in mice model of breast cancer (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_9393;
These findings suggest that Entresto confers cardiac protection against DIC in a mouse model of breast cancer without interfering with the antineoplastic effects of Dox. It underscores the potential clinical relevance of Entresto to enhance the safety and efficacy of doxorubicin-based cancer therapies.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
A small molecule Notch1 inhibitor (ASR490) restores chemosensitivity in triple-negative breast cancer (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_9301;
Hence, we postulated that pharmacologically targeting Notch1 in conjunction with a standard chemotherapeutic agent (Doxorubicin: DXR) may completely eradicate TNBC growth and overcome systemic and debilitating toxicity...In addition to being effective at inhibiting tumor growth, the significantly lower dose requirements of DXR and ASR490 in combination makes it a highly safe therapeutic modality. These findings suggest that aberrant activation of Notch1 is responsible for TNBC chemoresistance and concomitantly inhibiting Notch1 activation is an effective therapeutic strategy to restore chemosensitivity in TNBC.
- |||||||||| siremadlin (HDM201) / Novartis
ABCB1-mediated chemotherapeutic drug resistance is reversed by a potent p53-MDM2 inhibitor NVP-HDM201 (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_9296;
According to our findings, HDM201 significantly increased the sensitivity of ABCB1-overexpressing cells to ABCB1 substrates, such as colchicine and doxorubicin...Moreover, HDM201 promoted the accumulation of paclitaxel in cell lines that overexpress ABCB1...The computational support for the cross-reactivity of this p53 inhibitor with human ABCB1 comes from docking simulation results that align with the binding conformation of HDM201 within the vast cavity of the transmembrane region of ABCB1. In conclusion, by blocking the transport function of ABCB1, HDM201 can reverse ABCB1-mediated MDR in vitro.
- |||||||||| etoposide IV / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Investigation of the efficacy of duocarmycin SA in combination with FDA approved drugs in acute myeloid leukemia cells in vitro (Section 26) - Mar 5, 2024 - Abstract #AACR2024AACR_9286;
In summary, 1) picomolar concentrations of DSA alone was sufficient to significantly reduce AML cell viability; 2) DSA in combination with doxorubicin or etoposide significantly reduced AML cell viability and reduced the IC50 concentration of doxorubicin and etoposide. Thus, highlighting the therapeutic potential of using DSA in combination with doxorubicin or etoposide as a drug combination strategy to improve AML patient survival outcomes by decreasing the concentration of drugs necessary to treat patients and reducing off-target toxicity.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
ApoE genotype influences susceptibility to doxorubicin-induced cognitive impairment in juvenile rats (Section 39) - Mar 5, 2024 - Abstract #AACR2024AACR_9246;
Additionally, to determine the effect of DOXO treatment on ApoE4, we are investigating the role of mitogen-activated protein kinase (MAPK) signaling pathways within brain regions pertinent to memory and recognition. In summary, ApoE genotype contributes to differential susceptibility to CICI.
- |||||||||| pevonedistat (MLN4924) / Takeda, Keytruda (pembrolizumab) / Merck (MSD)
PDX models of TNBC established from pre- and post-therapy tumors identify vulnerabilities of resistant disease (Room 33 - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_8883;
P=N/A
Chemotherapy, along with the PD1 inhibitor pembrolizumab, is the recommended standard of care for patients with primary triple negative breast cancer (TNBC)...Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), after a 3-month course of additional chemotherapy and/or different experimental therapies in cases of AC resistance (post-NACT), and from the metastatic lesions of two patients...We found that post-NACT tumors exhibited enhanced sensitivity to drugs targeting protein homeostasis pathways. Preclinical studies with pevonedistat validated the neddylation pathway as an effective target in chemoresistant TNBC.
- |||||||||| Recentin (cediranib) / AstraZeneca, Tasigna (nilotinib) / Novartis, Inhibikase
Effect of antineoplastic drugs on cell-to-cell communication in the progression of colorectal cancer (Section 28) - Mar 5, 2024 - Abstract #AACR2024AACR_8122;
This enabled us to determine a foundational effect of these drugs on these cell lines, which had not been previously identified. Discovering this foundational effect will allow us to investigate the synergy effect when combined with gap junction enhancer by setting a baseline effect using these results.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Induction of the p-glycoprotein with atorvastatin using colorectal cancer cells (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_8065;
The experimental groups were treated with the statin drug, atorvastatin, at different concentrations and doxorubicin as the positive control, for 3-4 months...This study implicates that late-stage cancer patients, who are treated for hypercholesterolemia, may be at higher risk for developing chemotherapy-resistant tumor cells. With the identification of chemotherapy-resistant tumors in chemotherapy-na
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Retrotransposable elements mediate the drug-tolerant persistence in claudin-low breast cancer chemo-treatment (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_8047;
In the clinic, chemotherapy remains the mainstream treatment for TNBC, and one of the primary chemo-agents is doxorubicin...The preliminary result indicated that a subpopulation of HERV-high cells might transiently mediate the persistence of cancer cells at the early stage of the treatment, which coupled with whole transcriptomic and chromatin landscape reprogramming, and molecular subtype switching. In this study, we employed a new strategy to investigate the longitudinal adaptation route through treatment and uncover a non-canonical element, which shed new light on drug resistance research and novel target screening.
- |||||||||| N17350 / Onchilles Pharma
N17350 kills cancer cells, spares immune cells, and regresses CDX tumors from chemotherapy naive and experienced patients (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_8020;
In this study, we employed a new strategy to investigate the longitudinal adaptation route through treatment and uncover a non-canonical element, which shed new light on drug resistance research and novel target screening. Mice were treated with 2 doses of N17350 (400?g/100mm3, intratumoral) or carboplatin (100mg/kg, intraperitoneal), and effects on tumor growth were quantified...In contrast, doxorubicin and oxaliplatin showed similar toxicity to both cell types...Our data demonstrate that N17350 kills OvCa tumors in vitro and in vivo while sparing CD45+ immune cells in both chemotherapy na
- |||||||||| doxorubicin hydrochloride / Generic mfg.
SCUBE3 promotes therapy resistance in triple negative breast cancer (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_8017;
Unbiased high-throughput loss of function genomic screen was performed on breast cancer cells in the presence or absence of doxorubicin... Overall, our data suggests that SCUBE3 can be a potent therapeutic target for treating TNBC patients.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
ZNF451 and doxorubicin resistance (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_8015;
ZNF451 is an attractive target for future combination therapies with doxorubicin to induce conditional lethality. ZNF451 may be valuable to study as a prognostic biomarker for topoisomerase-II inhibitor chemotherapy.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Ultrasound-mediated nano-drug delivery system to enhance cancer treatment efficacy: An in vitro study (Section 22) - Mar 5, 2024 - Abstract #AACR2024AACR_7990;
ZNF451 may be valuable to study as a prognostic biomarker for topoisomerase-II inhibitor chemotherapy. We demonstrate a first-of-its-kind use of low-intensity pulsed ultrasound (LIPUS) to induce Doxorubicin release from the surface of gold nanoparticle drug carriers...We found that the LIPUS device operating at an acoustic power of around 4 W increased cell killing efficacy by approximately 15%
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Efficient and safe delivery of doxorubicin by DNA fragments: A full preclinical study (Section 20) - Mar 5, 2024 - Abstract #AACR2024AACR_7601;
DNA/DOX nanocomplexes are amenable to rigorous chemistry, manufacturing, and controls (CMC) evaluation with proven anti-cancer efficacy and improved safety profiles. Clinical trials on DNA/DOX nanocomplexes for cancer chemotherapy are warranted to fully validate their clinical utilities.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Non-invasive shortwave infrared imaging of cytotoxic T lymphocyte infiltration for monitoring responses to combination immunotherapy and chemotherapy (Section 9) - Mar 5, 2024 - Abstract #AACR2024AACR_7336;
After treating the mice with combination anti-PD-1 and doxorubicin, volumetric analysis of the mammary fat pad tumors did not show any significant impact of treatment compared to single treatment and untreated control mice...IHC staining of other immune markers, including CD45, CD3, CD4, and PD-L1, showed that combination treatment may influence in the expression of these markers, presenting additional targets that could be imaged with ReANCs in the future. In conclusion, the increase in SWIR signal from CD8-targeted ReANCs in tumors treated with combination immunotherapy and chemotherapy and the relationship with IHC staining highlight the ability to use SWIR imaging for non-invasive assessment of changes in immune dynamics following treatment.
- |||||||||| cyclophosphamide / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Small intestinal leiomyosarcoma in a young adult (Section 32) - Mar 5, 2024 - Abstract #AACR2024AACR_7206;
Treatment involves surgical resection and a cost benefit analysis of adjuvant chemotherapy with (Reynolds, 2014). This case of a 23 year old, without significant risk factors, diagnosed with a jejunal leiomyosarcoma presents as one of the youngest cases ever to be reported and emphasizes the importance of recognizing the cancer in a broader range of the adult population.
- |||||||||| SY-7021 / Shouyao Holdings
SY-7021, a novel DNA-PK inhibitor, exhibits significant anti-tumor activity in vitro and in vivo (Section 22) - Mar 5, 2024 - Abstract #AACR2024AACR_6877;
In addition, SY-7021 demonstrates good PK properties and acceptable safety profiles in in vivo studies. Collectively, SY-7021, a potent and selective DNA-PK inhibitor, shows significant inhibition on tumor growth in in vitro and in vivo studies, providing a rationale treatment for multiple tumors in monotherapy or in combination with other agents.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Identification of efficacy biomarkers for therapies targeting miR-10b (Section 29) - Mar 5, 2024 - Abstract #AACR2024AACR_6835;
Additionally, combination treatment with adjuvant doxorubicin induced a stable regression of metastases in immunocompromised and immunocompetent mouse models of metastatic TNBC...With our recent observation that the nanodrug inhibits miR-10b in metastases in vivo in as little as one dose after 72 hours, our next steps are to determine whether the cell differentiation-associated DEGs identified in RNA sequencing results can be used as biomarkers of nanodrug efficacy in vivo. Understanding the changes in gene expression induced by MN-anti-miR10b as a function of time will be critical for guiding treatment regimens in future preclinical and clinical trials.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics (Section 43) - Mar 5, 2024 - Abstract #AACR2024AACR_6552;
As proof of principle, we discover that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicin in vitro and in vivo using patient-derived xenograft (PDX) models. Our findings provide a valuable resource and demonstrate the feasibility of using targeted CRISPR knockout to discover combinations with common chemotherapeutics, a methodology with application across all cancers.
- |||||||||| MI-503 / Kura Oncology
Direct targeting of the COMPASS complex inhibits neuroblastoma growth by inhibiting cancer stem cells (Section 43) - Mar 5, 2024 - Abstract #AACR2024AACR_6549;
Our data show that MI-503 or MEN1 knockdown leads to significant inhibition of NB growth by directly inhibiting NB CSCs in both in vitro and in vivo tumor models. Further developing these epigenetic-based therapeutic strategies and combining them with current therapies will pave the way for effectively managing NB.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Targeting RNA demethylase ALKBH5 blocks growth and improves therapy response in osteosarcoma (Room 30 - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_6097;
Our results establish RNA demethylase ALKBH5 as a novel driver of OS. This project has a direct translational relevance as an FDA-approved drug can be repurposed for treating OS patients as a monotherapy or in combination with doxorubicin and be formally tested in the clinic without much delay.
- |||||||||| cisplatin / Generic mfg., doxorubicin hydrochloride / Generic mfg.
The ectopic expression of miR-380-5p interferes with the aggressive traits of diffuse malignant peritoneal mesothelima cells (Section 16) - Mar 5, 2024 - Abstract #AACR2024AACR_5738;
Moreover, a reduction of Vimentin and a slight increase in P-Cadherin protein levels were also observed in cells ectopically expressing miR-380-5p, likely indicating the occurrence of a reverse-EMT program. Finally, a pronounced increase in the sensitivity to Cisplatin and Doxorubicin was also appreciable in miR-380-5p- vs. preNeg-transfected cells, suggesting that miRNA-mediated induction of a reverse-EMT may, at least in part, contribute to improve the response of DMPM cells to chemotherapeutic drugs.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
SLC7A5/LAT1 promotes the Warburg Effect for TNBC progression through Trp/QPRT/NAD+ pathway (Section 19) - Mar 5, 2024 - Abstract #AACR2024AACR_5705;
Additionally, we found upregulations of SLC7A5/LAT1, p-PKM2 and p-LDHA in doxorubicin-resistant cells and PDX mouse model compared with their corresponding controls...Our ongoing work will evaluate whether inhibiting LAT1 genetically or pharmacologically reduces xenograft tumor growth and enhances the sensitivities of TNBC resistant cells to chemotherapy in vivo. Our investigation will elucidate the underlying mechanisms involved in these processes.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Anti-diabetic drug, semaglutide, prevents doxorubicin-induced endothelial cell toxicity (Section 15) - Mar 5, 2024 - Abstract #AACR2024AACR_5636;
Inconclusion, our current results suggests that the anti-diabetic drug, Semaglutide, could prevent Dox-induced endothelial cell death by regulating the expression of various pro-apoptotic, anti-apoptotic and inflammatory markers. Thus, our data indicate that Semaglutide could be used as a potential adjuvant drug to reduce the adverse effects of anthracycline chemotherapeutic drugs.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Deciphering the role of miRNA146-a and its crosstalk with cellular redox state in senescence escape in breast cancer cells (Section 15) - Mar 5, 2024 - Abstract #AACR2024AACR_5626;
Interestingly, these changes coincided with a significant increase in miR-146 expression (during senescence), which was previously shown to downregulate ROS in other model systems. While modulating miR-146a did not seem to change ROS levels upon doxorubicin-induced senescence in MDA-MB231 cells, the precise crosstalk between cellular ROS, miR146-a and senescence evasion is currently being pursued.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Antitumor activity of a coencapsulated liposomal formulation of ceramides and doxorubicin in neuroblastoma models (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_5338;
Our preliminary findings demonstrate that the co-encapsulation and delivery of C6-Ceramide and DXR by NCL-recognizing nanoparticles exert potent antitumor effects against NB models in vitro. Ongoing in vivo experiments on clinically relevant mouse NB models (i.e. recapitulating primary tumor growth, metastases, and minimal residual disease) will allow us to define the possible use of F3-NC[C6-Cer/DXR] as an innovative therapeutic strategy for relapsed/refractory NB.
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