Current cancer drug targets最新文献

Introduction/objective: Nano-curcumins (Nano-CUR) improve solubility, bio-availability, and stability of the release of CUR into the body. In this systematic review, we aim to investigate different CUR nanoformulations' in targeting radiosensitizing path-ways and radioprotective mechanisms.

Methods: We thoroughly searched electronic databases, including PubMed/MEDLINE, Web of Science, Scopus, Embase, and Cochrane Library to identify pertinent studies pub-lished before July 21, 2024. inclusion and exclusion criteria were set based on the study's purposes. Two reviewers independently performed data extraction to ensure precision and minimize bias. Subsequently, the data were extracted and analyzed.

Results: A total of 24 articles were included. Nano-CURs by scavenging the levels of re-active oxygen species (ROS), decrease malondialdehyde (MDA), improve superoxide dismutase (SOD), prevent DNA methylation, reduce tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-b and transforming growth factor-beta (TGF-β1), improve cell cycle, inhibit vascular endothelial growth factor (VEGF), attenuate cell cytotoxicity and modu-late cell apoptosis induce its radioprotective effects. In contrast, Nano-CUR induces oxida-tive stress and accumulation ROS, inhibits nuclear factor-κB (NF- κB), activates the ex-pression of TNF, TGF-β, phosphatidylinositol and FoxO, causing DNA damage, activat-ing proapoptotic pathways (boosted P53, P21 and BAX expressions), cell cycle arrest, re-ducing hypoxia-inducible factor (HIF-1α), revealed radiosensitizing effects.

Conclusion: Nano-CURs improve CUR bioavailability and increase cancerous cells' sen-sitivity to radiation. They also protect healthy cells from ionizing radiation without signifi-cant side effects.

Background: Historically, there has been a lack of focus on the mortality rates of individuals with both diabetes and Bladder Bancer (BC). Our study aimed to identify the risk factors associated with death from Diabetes Mellitus (DM) in BC patients.

Methods: Data was gathered from the SEER database on individuals who were diagnosed with BC between the years 2000 and 2017. Calculation of the Standardized Mortality Ratio (SMR) was performed to determine the mortality rate of DM in patients from BC. Potential risk factors for DM mortality were identified by a multivariate competing risk model. Haz-ard Ratios (HR), with 95% confidence intervals (95% CI) were used to indicate the degree of associated risk.

Results: A total of 217,230 BC patients' data were collected from the SEER database for analysis. Among them, 98,880 patients passed away, and 1,783 patients encountered DM mortality. The overall SMR for DM mortality in BC patients was 3.32 (95% CI: 3.17-3.48). Results indicated that SMR increased with increasing years but decreased with increasing follow-up time. Multivariate competing risk analysis shows that BC patients with the fol-lowing factors were at higher risk of developing DM mortality: advanced age, male, black, in situ tumor stage, early year of diagnosis, pathology type of transitional cell carcinoma, without chemotherapy or radiation therapy, and absence of spouse (including separated, di-vorced, widowed, and unmarried).

Conclusion: Individuals diagnosed with BC are at a considerably elevated risk of mortality from DM compared to the general population. It is of the utmost importance to identify high-risk groups and implement effective interventions for DM in order to enhance the sur-vival rate among this patient population.

Among the Poly(ADP-ribose) Polymerase (PARP) family in mammals, PARP1 is the first identified and well-studied member that plays a critical role in DNA damage repair and has been proven to be an effective target for cancer therapy. Here, we have reviewed not only the role of PARP1 in different DNA damage repair pathways, but also the working mech-anisms of several PARP inhibitors (PARPi), inhibiting Poly-ADP-ribosylation (PARylation) processing and PAR chains production to trap PARP1 on impaired DNA and inducing Tran-scription-replication Conflicts (TRCs) by inhibiting the PARP1 activity. This review has sys-tematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer. Furthermore, probable challenges in PARPi application and drug resistance mechanisms have also been discussed. Despite these challenges, further development of new PARP1 inhibitors appears promising as a valuable approach to cancer treatment.

The ubiquitin-proteasome system is a fundamental regulatory mechanism that governs protein stability and intracellular signaling in eukaryotic cells. This system relies on a coordinated cascade of enzymatic activities involving activating enzymes, conjugating enzymes, and ligases to assemble distinct ubiquitin signals. These signals are subsequently edited, removed, or interpreted by deubiquitinases and ubiquitin-binding proteins. While E3 ligases have traditionally been recognized as the primary determinants of substrate specificity in the ubiquitination process, recent studies have revealed that the dysregulation of E2 enzymes can also lead to significant pathological outcomes, including chromatin instability, immune dysregulation, metabolic dysfunction, and an elevated risk of cancer. Consequently, E2 enzymes have emerged as promising therapeutic targets for the treatment of various dis-eases. This review provides a comprehensive examination of the roles and mechanisms of the ubiquitin-conjugating enzyme E2T (UBE2T) in cancer initiation, progression, and therapy resistance, highlighting its potential as a compelling target for cancer therapeutics.

Biotechnology has paved the way for the development of cancer therapeutics that harness biological systems. Cancer immunotherapy (CI) is a pivotal and swiftly progressing therapeutic modality, alongside surgical intervention, cytotoxic chemo-therapy, radiation therapy, and targeted therapy. Therefore, this is the fifth cornerstone of cancer management. Biotechnological pharmaceuticals are superior modalities for combat-ing neoplastic conditions when juxtaposed with conventional chemical therapeutics. Consid-ering empirical evidence, it can be posited that biotechnology exhibits a heightened level of precision in targeting malignant cells associated with cancer, thereby minimizing collateral damage compared to conventional chemotherapeutic approaches. Furthermore, this ap-proach harnesses the inherent capabilities of the immune system to impede cancer recur-rence, thereby facilitating a more proactive therapeutic intervention, as opposed to a mere deleterious remedy. Novel cancer immunotherapeutic medications, along with uncomplicat-ed methodologies that enable the quantitative evaluation of the effectiveness of compounds capable of modifying T cell-mediated, tumor antigen-specific immune responses, play a pivotal role in the assessment process. This highlights the considerable promise of immuno-therapies, monoclonal antibodies, and an array of biotechnological products in a relentless battle against cancer.

Introduction: Breast Cancer (BC) is one of the most prevalent malignant tumors in women. The incidence of estrogen receptor-positive (ER+) breast cancer is as high as 70%, and it is increasing. Amorphophalli rhizoma (APR) has the potential to be used in breast cancer.

Aims: The objectives of the present study were to explore the impact of different APR extracts on the proliferation, migration, and invasion of ER+BC and to investigate their possible mechanism at the molecular level.

Methods: Various extracts of APR were prepared in different solvents, such as petroleum ether, ethyl acetate, n-butanol, and water. ER+ T47D breast cancer cell lines were acquired and uti-lized to assess the effect of APR extracts on ER+ BC. Cell viability was assessed using the cell counting kit8 (CCk8) method, while anti-invasive and migratory effects were examined by transwell and wound healing assay. All the extracts were initially screened, and the ethyl acetate fraction (APR-EA) was found to be the most effective. Ultra High-Performance Liquid Chro-matography (UHPLC) of APR-EAE extract revealed the presence of various phytochemicals, such as succinic acid, 2-methoxy resorcinol, penicillic acid, morphine, salicylic acid, α-linolenic acid, and linolenic acid. Flow cytometry, western blot, and immunohistochemistry were used to explore molecular mechanisms.

Results: APR-EA demonstrated anti-proliferative, anti-migratory, and anti-invasive effects on the ER+ T47D cell line. Thus, APR-EAE might inhibit the expression of P-PI3K/PI3K and P-Akt/Akt proteins, which subsequently represses the expression of ERα. This inhibition affects the downstream expression of the proteins CDK4 and Bcl-2, which are linked to cell growth and apoptosis.

Conclusion: Additionally, APR-EA might increase the expression of P21 and Bax proteins, which are associated with cell cycle arrest and apoptosis. Overall, these effects contribute to the anti-ER+ breast cancer properties of APR-EA.

Recent investigations have indicated that circRNAs (circular RNAs), a novel member of the Noncoding RNA family, are a crucial genetic factor in Colorectal Cancer (CRC), development. These circRNAs have a range of biological functions, including regu-lating the expression of target genes, altering protein activity, and producing proteins. Addi-tionally, circRNAs significantly affect tumor cell proliferation, aggression, migration, and cell death. CircRNAs have an essential role in carcinogenesis, metastasis, and drug toler-ance. Various signaling pathways are linked by circRNAs, providing opportunities for a more tailored chemotherapy regimen as well as early diagnosis and prognosis determination. By identifying new and potent circRNAs in signaling pathways, we can aim for them with ASO or siRNAs and provide a powerful combination therapy. In this review, we strive to summarize the biological and carcinogenic functions of circRNAs and their impact on spe-cific signaling pathways like PI3K/AKT, MAPK, Notch, JAK/STAT, Hippo/YAP, and WNT/β-catenin which lead to Epithelial-mesenchymal-transition(EMT) in CRC. Further-more, we explore the clinical significance of circRNAs and important signaling proteins in treating CRC.

Background: Quinoline derivatives, often incorporating other heterocyclic structures, have shown a wide range of therapeutic potential, especially in the treatment of cancer. These compounds have demonstrated significant anticancer activity against various cell lines, including HeLa (human cervical cancer) and MDA-MB-435 (melanoma), exhibiting strong inhibitory effects.

Objective: In this study, arylhydrazonopyrazole derivatives (3a-c) were employed in a series of multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinoline and pyran derivatives. Pyrazolo[1,5-a]quinoline derivatives, due to their structural properties, are considered valuable scaffolds for the development of novel drugs targeting similar biological pathways, with the potential for improved therapeutic efficacy. This study aimed to demonstrate the use of simple arylhydrazonopyrazole derivatives in multicomponent reactions with cyclic ketones and aromatic aldehydes. The resulting compounds were then assessed for their cytotoxic and antiproliferative activities. Following these reactions, further heterocyclization processes were conducted, incorporating the quinoline moiety into the final structures. These findings underscore the potential of pyrazolo [1,5-a]quinoline derivatives as promising candidates for drug discovery, offering new avenues for targeting diseases with related molecular mechanisms.

Methods: The key starting compound in this study was 3,5-dimethyl-4-(2-phenylhydrazono)-4H-pyrazole, which has been utilized in numerous heterocyclization reactions. These reactions, involving various reagents, such as cyclic ketones and diketones in the presence of aromatic aldehydes, led to the formation of fused tetracyclic compounds. Arylhydrazonopyrazole derivatives (5a-c) were employed in multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinoline and pyran derivatives. The reactions were carried out using both conventional catalysts and ionic liquid-immobilized catalysts. Notably, the use of ionic liquid-immobilized catalysts resulted in higher yields of the desired compounds.

Results: In this study, new compounds were synthesized, characterized, and evaluated for their cytotoxicity against six cancer cell lines: A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Additionally, the cytotoxic effects of the synthesized compounds were assessed against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cell lines. Morphological studies of selected compounds were also conducted to further understand their effects on the cancer cells. Moreover, the cytotoxicity of the selected compounds was tested against seventeen different cancer cell lines, categorized by disease type. Morphological analyses of these selected compounds were also performed to gain deeper insights into their potential as anticancer agents.

Conclusion: