Recent Patents on Anti-Cancer Drug Discovery - Online First

Esophageal cancer is a common malignant tumor, making the search for effective treatments a critical research focus. L-methylselenocysteine (L-SeMC) has been reported to exert anticancer effects in various cancers; however, its role and underlying mechanisms in esophageal cancer remain unclear. This study aimed to investigate the anticancer effects of L-SeMC on esophageal cancer both in vitro and in vivo, and to explore its potential mechanisms of action.

For cellular studies, flow cytometry, colony formation assay, MTT assay, wound healing assay, and ROS measurement were employed. Western blotting was used to assess the expression levels of apoptotic proteins. A subcutaneous tumor xenograft model was established. The analysis included the evaluation of proteins related to the PI3K/AKT signaling pathway, TUNEL, and Ki-67 staining, as well as HE staining.

L-SeMC caused cell death and, in a concentration-dependent manner, reduced the migration, invasion, and proliferation of esophageal cancer cells. Western blot analysis showed that L-SeMC was associated with a decrease in the anti-apoptotic protein Bcl-2 and an increase in the pro-apoptotic protein Bax. It also triggered the mitochondrial apoptosis pathway, promoting the activation of caspase-3 and subsequent cancer cell death induced by L-SeMC. In a dose-dependent manner, L-SeMC decreased the phosphorylation of phosphatidylinositol 3-kinase (PI3K) downstream effector molecules. This suggests that L-SeMC inhibits the PI3K/AKT signaling pathway in esophageal cancer cells, contributing to its anticancer effects.

L-SeMC has a strong anticancer effect on human esophageal cancer cells and promotes apoptosis by inhibiting the PI3K/AKT signaling pathway, suggesting that L-SeMC may represent a novel strategy for the treatment of esophageal cancer.

Immunotherapy and targeted therapy have been shown to be notably effective in tumor treatment; however, the mechanism of PTEN function in tumorigenesis, development, and immune response of tumors remains unclear.

We show that PTEN expression varies significantly in many types of tumors and affects the prognosis of patients with cancer using pan-cancer analysis. Patents were reviewed using the World Intellectual Property Organisation database. We analyzed data from GTEx, CCLE, and TCGA to study the correlation between PTEN expression and prognosis, investigated the correlation between PTEN expression and tumor-infiltrating immune cells using TIMER, analyzed the mutation pattern of PTEN and its correlation with neoantigen expression, TMB, MSI, MMRs, and DNA methyltransferases in tumors, and conducted an enrichment analysis of PTEN in tumors using GSEA.

PTEN expression is related to the levels of infiltrating immune cells, such as B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. PTEN expression is closely related to neoantigen expression, tumor mutational burden, microsatellite instability, and mismatch repair. The results of a functional enrichment analysis of PTEN showed that PTEN has the potential as a biomarker for precision immunotherapy of tumors.

This study suggests that PTEN may be involved in the recruitment and regulation of immune-infiltrating cells, tumor development, metastasis, prognosis, tumor immune escape, and immunotherapy, indicating its importance in tumor diagnosis and treatment.

Colorectal cancer is a significant global public health challenge, contributing substantially to cancer-related mortality worldwide. Vitexin has been shown to promote the polarization of macrophages towards the M1 phenotype, a process dependent on the Vitamin D receptor. This polarization is crucial in the tumor microenvironment, as it helps mitigate the progression from chronic colitis to colorectal cancer. Despite its potential, the mechanisms of vitexin’s action and its impact on colon cancer remain unclear.

This study aims to evaluate the inhibitory effects of vitexin on cell proliferation and apoptosis in the Caco-2 colon cancer cell line, with a specific focus on its modulation of antioxidant enzyme activities, pro-apoptotic factors, and key signaling pathways involved in cell survival and proliferation.

The IC50 of vitexin against Caco-2 cells was determined. Cell viability and necrosis rates were assessed after 48 hours of incubation with vitexin at concentrations of 19.01, 38.01, and 76.02 µg/mL. Additionally, levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), P53, Bax, TSC2, Sestrin 2, and PUMA, as well as the expression of AMPK, PI3K, Akt, and mTOR genes and proteins, were measured using q-PCR and Western blotting techniques in Caco-2 cells post-incubation.

Vitexin exhibited an IC50 of 38.01 ± 0.64 µg/mL against Caco-2 cells. Treatment with vitexin at the specified concentrations for 48 hours resulted in a significant decrease in cell viability by 28.40%, with inhibitory rates reaching 71.6%. Apoptosis rates increased to 93.81%, 171.41%, and 294.12%, respectively, with a corresponding rise in necrosis rates by 194.19%, 400.22%, and 811.44%. Pharmacological analysis revealed that vitexin significantly inhibited SOD and CAT activities while enhancing MDA production. Furthermore, vitexin treatment upregulated the expression of key apoptotic markers (P53, Bax, TSC2, Sestrin 2, and PUMA) and the expression of AMPK, PI3K, and Akt, while downregulating mTOR genes and proteins, implicating various signaling pathways.

This study demonstrates that vitexin induces apoptosis in Caco-2 colon cancer cells through multiple mechanisms, including modulation of antioxidant enzymes, upregulation of pro-apoptotic factors, and regulation of key signaling pathways involved in cell survival and proliferation. These findings suggest that vitexin’s mechanisms of action involve complex interactions with various cellular pathways, making it a promising candidate for further research and potential therapeutic applications in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide, and its occurrence and progression are often regulated by genetic and hereditary factors. Ubiquitination and the associated ubiquitin-binding enzymes and ligases regulate the tumor microenvironment and antitumor immunity to mediate tumor pathogenesis and progression. In this study, we examined the molecular characteristics and immunomodulatory effects of ubiquitination-associated genes that mediate CRC prognosis.

The ubiquitination-related gene ubiquitin domain-containing protein 1 (UBTD1) was identified using bioinformatics and single-cell analyses. Subsequently, the ability of UBTD1 to predict CRC prognosis and immune checkpoint correlation was analyzed, the potential drug telatinib targeting UBTD1 was explored, and the correlation between UBTD1 and ferroptosis was analyzed. The role of UBTD1 in CRC and ferroptosis was verified using immunohistochemistry, gene knockout, western blot, cell cloning, and immunofluorescence.

UBTD1 was identified as a significant prognostic and predictive gene for CRC and was involved in regulating immune checkpoint levels and immune cell function of CRC patients with CRC. High UBTD1 expression was found to enhance the presence of immune checkpoints that induce immune escape and inhibit ferroptosis onset. Telatinib may be a potential therapeutic drug targeting UBTD1.

Our study demonstrated that UBTD1 is a prognostic marker for CRC in the regulation of ubiquitination and the tumor immune microenvironment and may serve as a modulator of ferroptosis.

This study aimed to explore the clinical efficacy and safety of durvalumab combined with albumin-bound paclitaxel and carboplatin as neoadjuvant therapy for resectable stage III Non-small Cell Lung Cancer (NSCLC).

A single-arm open-label phase Ib study was conducted. A total of 40 patients with driver gene-negative resectable stage III NSCLC were enrolled. All patients received neoadjuvant treatment with durvalumab in combination with albumin-bound paclitaxel and carboplatin. The clinical efficacy, Major Pathological Response (MPR), Complete Pathological Response (pCR), and safety were assessed. Flow cytometry was used to detect the expression of programmed cell death receptor 1 (PD-1) on total T, helper T, and cytotoxic T lymphocytes in peripheral blood before and after neoadjuvant treatment. Adverse reactions during the treatment were recorded. Disease-free Survival (DFS) and Overall Survival (OS) curves were constructed.

After the neoadjuvant treatment, the overall Objective Response Rate (ORR) in the 40 patients with NSCLC was 65.00%. MPR was achieved in 27 patients (67.50%), and pCR was achieved in nine patients (22.50%). The expression levels of PD-1 on total T, helper T, and cytotoxic T lymphocytes in patients with NSCLC significantly decreased after treatment (all p < 0.05). The most common adverse events were hair loss (47.50%), nausea and vomiting (42.50%), and fatigue (40.00%). The majority of adverse events were grades 1 and 2, with a small number of events being grades 3 and 4. At the end of the follow-up period, the average DFS was 21.49 ± 0.99 months, and the average OS was 24.79 ± 0.53 months.

Neoadjuvant treatment with durvalumab combined with albumin-bound paclitaxel and carboplatin as first-line therapy for driver gene-negative stage III NSCLC achieved a high pathological response rate and improved immune function. It is expected to extend patient survival with good tolerability.

Lysyl oxidase-like 2 (LOXL2) is a metalloenzyme that catalyzes oxidative deamination ε-amino group of lysine. It has been found that LOXL2 is a promotor for the metastasis and invasion in kinds of tumors. Previous studies show that disulfide bonds are important components in LOXL2, and their bioactivity can be regulated by those bonds. In this way, a small molecule covalently binds to the thiol group of cysteine residue could be an effective way to change the function of LOXL2 by blocking the formation of the disulfide bond.

This investigation is aiming to screen covalent inhibitor for LOXL2.

Covalent molecule libraries of Life Chemical and Enamine were used. The structures of those molecules were optimized by using LigPrep module of Schrödinger. Then optimized by using the LigPrep module of Schrödinger to generate optimal conformations. For covalent docking, CovDock in Glide module was used for the virtual screening. Finally, wound-healing assays were performed to examine the effects of the potential inhibitors.

Eight potential small molecules were selected by covalent docking from the databases (in total 7,908 candidates). ADMET evaluation indicated that all those eight small molecules satisfy the general standard. Furthermore, wound healing experiments showed that the compound (F50972176) significantly inhibits the migration of cancer cells.

Virtual screening and experimental verification methods were used to screen covalent inhibitors of LOXL2 by targeting functional disulfide bonds. The compound (F50972176) effectively inhibited the migration of esophageal squamous cell carcinoma cells.

Chronic hepatitis B virus (HBV) infection remains a major global public health problem with devastating consequences, such as hepatocellular carcinoma. Currently, approved treatments are limited to interferon and nucleoside/nucleotide analogues for chronic hepatitis B and chemotherapy, radiotherapy, and surgery for cancer. Both treatments have their limitations, making complete cure an elusive goal. Therefore, the identification of new therapeutic targets using medicinal plants and the development of new antiviral and anticancer strategies are of utmost importance.

The aim of this review is to identify from the literature the substances and molecules of West African flora involved in the fight against chronic hepatitis B and liver cancer and to provide a summary of their mechanisms of action.

Pubmed, HAL open science, and Google Scholar literature search engines were used to identify medicinal plants and molecules from the West African flora.

Among West African countries, Gambia and Niger had the highest prevalence of hepatitis B virus infection, and 09 West African countries had high rates of liver cancer. A number of studies carried out in Mali, Benin, Senegal, and Burkina Faso enabled us to list anti-HBV and anticancer plants, as well as a number of molecules isolated from plants found in West African regions.

By offering a glimpse into the world of anti-HBV and anticancer molecules from West Africa, this review provides valuable information to support the future development of herbal antiviral and anticancer drugs.