Recent research on cancer
Malignant tumors(cancers) are one of the major health problems posing a serious threat to human health, and for many years, human beings have been continuously conducting research on anti-tumor drugs.
1. Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial
Diffuse high-grade glioma (HGG) is a refractory brain tumor, and even with standard-of-care (SOC) treatments such as maximal surgical resection, local radiotherapy, and chemotherapy, tumor growth cannot be effectively controlled. Glioblastoma (GBM) is the most aggressive and has the poorest prognosis among HGG types. Even with intensified SOC treatment, the tumor still recurs, and there is currently no effective treatment method, resulting in a high mortality rate for patients.
CAR-T cell therapy has been used in early clinical trials to improve the treatment outcomes of HGG. Currently, research has shown that CAR-T therapy can target a range of tumor-associated antigens in gliomas, such as IL-13Rα2, HER2, EGFRvIII, GD2, and B7H3, and has achieved some success.
On March 7, 2024, researchers published a paper in the journal Nature Medicine, which demonstrated that local IL-13Rα2-targeted CAR-T therapy is safe and exhibits promising clinical activity in some patients.
IL-13Rα2 is a cancer-testis antigen, and the majority of glioblastomas (GBM) express this antigen, which is associated with mesenchymal gene features and poor prognosis in GBM. Since IL-13Rα2 is not expressed in normal brain tissue, it has great potential as a CAR-T target. In this research paper, the authors reported the results of a Phase I trial of IL-13Rα2-targeted CAR-T cell therapy for recurrent glioblastoma (rGBM) and other high-grade gliomas (HGG). This is the largest clinical study completed to date and the most extensive evaluation of CAR-T cells delivered directly to brain tumors.
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2. Small-molecule inhibition of MAP2K4 is synergistic with RAS inhibitors in KRAS-mutant cancers
KRAS, as one of the commonly mutated oncogenes in human cancer, promotes and sustains tumor formation by enhancing cell proliferation and evading apoptosis. To date, the FDA has approved two KRASG12C-targeted inhibitors (#Adagrasib, #Sotorasib) for the treatment of cancers such as lung cancer and pancreatic cancer.
KRASG12C inhibitors have shown clinical responses in KRASG12C-mutant lung cancer, but much less so in colon cancers having the same mutation. In lung cancer, acquired resistance limits the clinical benefit patients experience.
In the latest issue of #PNAS, a research team from the Netherlands Cancer Institute has discovered that the combination of a KRAS G12C inhibitor and a MAP2K4 inhibitor—HRX-0233?can effectively block the activation of KRAS. This strategy provides a new therapeutic approach and potential for treating KRAS-mutant cancers. It is the first time that the synergistic effect of a MAP2K4 inhibitor with a RAS inhibitor has been demonstrated in cancer.
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3. SLC25A51 decouples the mitochondrial NAD+/NADH ratio to control proliferation of AML cells
In the process of tumorigenesis, many cancer cells heavily rely on mitochondrial oxidative metabolism to sustain their rapid proliferation. Therefore, targeting mitochondrial function is also a direction for cancer therapy.
Taking acute myeloid leukemia (AML) as an example, AML cells exhibit a high dependence on mitochondrial metabolism processes such as oxidative phosphorylation and fatty acid oxidation, and mitochondrial dysfunction may affect the development and therapeutic efficacy of AML.
In a recent issue of Cell Metabolism, scientists discovered elevated levels of a cell transporter protein called SLC25A51 in AML patients with poor prognosis. In healthy cells, this transporter protein is responsible for providing energy for cellular processes. However, in AML cells, its increased levels act like stepping on the accelerator, driving cell replication into a state of hyper-speed. Lowering the levels of SLC25A51 can control disease progression.
Currently, a therapeutic challenge for some AML patients is the limited efficacy of single-agent treatment with Azacytidine, resulting in low response rates and survival rates. Therefore, researchers investigated whether SLC25A51 could be combined with AML therapeutic drugs to enhance efficacy.
In vitro experiments were conducted first, treating U937 cells to determine their IC50 for 5-azacytidine. It was found that depletion of SLC25A51 rendered U937 cells more sensitive to 5-azacytidine treatment in a dose-dependent manner. Subsequently, in mouse models, depletion of SLC25A51 in combination with 5-azacytidine treatment led to a reduction in tumor burden, a decrease in the percentage of leukemia cells in the bone marrow, and a decrease in spleen weight and infiltrative tumor cells. Moreover, it also extended the overall survival time of the mice.
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TargetMol is always at the forefront of cancer-focused research. We provide?comprehensive resources, including anti-tumor related small molecules,?compound libraries, recombinant proteins, and antibodies to support antitumor?drug discovery. We also provide computer-aided drug discovery?(CADD) services tailored for your research on cancer-related drug screening.
Numerous products related to cancer can be found in TargetMol:
1. Compound libraries (parts):
L2100 Anti-Cancer Compound Library ?Anti-Cancer Compound Library | TargetMol
L2160 Anti-Cancer Active Compound Library Anti-Cancer Active Compound Library | TargetMol
L6700 Anti-Tumor Natural Product Library Anti-Tumor Natural Product Library | TargetMol
L2150 Anti-Cancer Drug Library Anti-Cancer Drug Library | TargetMol
L2110 Anti-Cancer Approved Drug Library Anti-Cancer Approved Drug Library | TargetMol
L2120 Anti-Cancer Clinical Compound Library Anti-Cancer Clinical Compound Library | TargetMol
L2130 Anti-Cancer Metabolism Compound Library Anti-Cancer Metabolism Compound Library | TargetMol
2. Tool compounds (parts):
T1765 Erastin ?Erastin | Ferroptosis activator | TargetMol
T1564 Cisplatin ?Cisplatin | Ferroptosis | DNA Alkylator/Crosslinker | DNA/RNA Synthesis | Autophagy | TargetMol
T1020 Doxorubicin hydrochloride Doxorubicin hydrochloride | HIV Protease | Antibacterial | Topoisomerase | Antibiotic | Autophagy | AMPK | Apoptosis | Mitophagy | HBV | TargetMol
T1537 Rapamycin Rapamycin | Inhibitor | Antibiotic | Endogenous Metabolite | Antifungal | mTOR | Autophagy | TargetMol
T8689 CHLOROQUINE Chloroquine | HIV Protease | Antibiotic | Parasite | SARS-CoV | TLR | Autophagy | TargetMol
3. Proteins (parts):
TMPY-00996 PD-1 Protein, Mouse, Recombinant (His) PD-1 Protein, Mouse, Recombinant (His) | TargetMol
TMPY-00897 PD-1 Protein, Human, Recombinant (His) PD-1 Protein, Human, Recombinant (His) | TargetMol
TMPY-05208 PD-L1 Protein, Human, Recombinant PD-L1 Protein, Human, Recombinant | TargetMol
TMPY-01155 PD-L1 Protein, Mouse, Recombinant (His) PD-L1 Protein, Mouse, Recombinant (His) | TargetMol
TMPY-00742 EGFR Protein, Human, Recombinant (His) EGFR Protein, Human, Recombinant (His) | TargetMol
4. Antibody (parts):
T9917 Denosumab??Denosumab | RANKL/RANK | TargetMol
T9918 Daratumumab??Daratumumab | Inhibitor | TargetMol
T9907 Nivolumab??Nivolumab | PD-1/PD-L1 | TargetMol
T9904 Bevacizumab??Bevacizumab | VEGFR | TargetMol
T9905 Cetuximab??Cetuximab | EGFR | TargetMol
More product information, please visit: https://www.targetmol.com/