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Targeted drug combination therapy design based on driver genes.

Targeted therapies against cancer types with more than one driver gene hold bright but elusive promise, since approved drugs are not available for all driver mutations and monotherapies often result in resistance. Targeting multiple driver genes in different pathways at the same time may provide an impact extensive enough to fight resistance. Our goal was to find synergistic drug combinations based on the availability of targeted drugs and their biological activity profiles and created an associated compound library based on driver gene-related protein targets. In this study, we would like to

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… Targeting actually present versus absent driver genes Prior to the combination studies we conducted an experiment on the HCT116 cell line to explore the difference between the effectiveness of the compounds of the DriverHit Library on the actually present driver-related proteins and molecules having … According to this, the first group of targeted proteins were products of driver genes associated with HCT116, whereas the second cohort of targets were not involved in the pathologic proliferation of HCT116 cells. We performed an unpaired t -test using the pIC 50 values of the compounds. …

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

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… Huang et al. [ 133 ] demonstrated that the CRC cell line HCT116 was resistant to 5‐FU or oxaliplatin and that parental HCT116 cells cultured in spheroids showed a greater number of CD133 + and CD44 + cells than parental HCT116 cells cultivated in monolayers. … Moreover, inhibition of the Notch pathway reduced the growth of HCT116 cells resistant to 5‐FU or oxaliplatin and parental HCT116 cells cultured in spheroids in in vitro and in vivo models. …

Unveiling the Role of CCL3: A Driver of CIPN in Colon Cancer Patients?

Cancer neuroscience is an emerging field revealing how malignancies interact with the nervous system to shape disease progression and symptom burden. In colorectal cancer (CRC), increasing evidence suggests a direct interplay between tumor cells and peripheral sensory neurons, contributing not only to cancer progression but also to chemotherapy-induced side effects such as peripheral neuropathy. Chemokines, particularly CCL3, appear to be key players in this bidirectional communication. This literature review aims to critically examine the role of CCL3 in CRC and chemotherapy-induced periphera

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… This has driven the authors to investigate the role of CCR5 in CRC progression and found the Erk, PI3K, AKT intracellular pathways to be phosphorylated in the HCT116 cells after CCL5 treatment (HCT116-CCR5). …

Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells.

Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment. Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged a

Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of

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… Therefore, the ability of Calebin A to down-regulate the major inflammatory transcription factor NF-κB and its genetic end products in HCT116 cells, both when NF-κB was TNF-α or TNF-β induced, seemed very promising for further research. …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

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… cell lines | 0, 1, 2, and 4 μM for 12h | Inhibits USP14, inactivates the GPX4, while increasing GSH depletion and reducing SLC7A11 expression levels | Li et al. ( 113 ) Resveratrol | Peanuts, pistachios, bilberries and blueberries | CRC HT29 and HCT116 cells | The IC50 values: 47.85±0.96 µg/ml in HT29 … Yang Y et al. discovered that PL enhanced cancer cell ferroptosis by inhibiting TXNRD1 in colon cancer cells HCT116 cells ( 126 ). …

Identification of the sAPRIL binding peptide and its growth inhibition effects in the colorectal cancer cells.

BackgroundA proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) super family. It binds to its specific receptors and is involved in multiple processes during tumorigenesis and tumor cells proliferation. High levels of APRIL expression are closely correlated to the growth, metastasis, and 5-FU drug resistance of colorectal cancer. The aim of this study was to identify a specific APRIL binding peptide (BP) able to block APRIL activity that could be used as a potential treatment for colorectal cancer.MethodsA phage display library was used to identify peptides tha

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… The rate of proliferation was significantly inhibited ( p< 0.05) by treatment with sAPRIL-BP in LOVO and HCT116 cells ( Fig 3A ) in a time- and dose-dependent manner. However, this was not the case in SW620 and HT-29 cells ( Fig 3B ). … (A) APRIL high LOVO and HCT116 cells and (B) APRIL low SW620 and HT-29 cells were treated with the indicated doses of sAPRIL binding peptides for 24, 48, and 72 h, and proliferation was determined using the CCK-8 kit. …

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

Протекционный субъект PSMD1 является ключевой терапевтической целью в множестве миеломы.

Мы пришли к выводу, что PSMD1 - ключевой субъект протеиновой регуляционной частицы 19S - был чрезмерно экспрессирован и коррелировал с плохим прогнозом в множестве миеломы (ММ). Генетическое истощение PSMD1 снизило жизнеспособность раковых клеток, вызвало поликутилизированное накопление белка и способствовало апоптозу. Протеомический анализ показал активацию иммунных путей, что свидетельствует о потенциале иммунной модуляции. Нацеливание PSMD1 на незначительную поражающую РНК (SIRNA), доставляемую через липидные наночастицы (LNPs), уменьшило рост опухоли в линиях клеток MM и первичных проб пац

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

Nostoc commune-derived scytonemin induced mitochondrial cell death in leukemia models.

Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC50 values ranging

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… HCT116 cells were cultured in a RPMI 1640 medium (Biosera, Kansas City, MO, USA) supplemented with 10% FBS and 1% penicillin/streptomycin solution. …

CRISPR/Cas9: A revolutionary genome editing tool for human cancers treatment.

Cancer is a genetic disease stemming from genetic and epigenetic mutations and is the second most common cause of death across the globe. Clustered regularly interspaced short palindromic repeats (CRISPR) is an emerging gene-editing tool, acting as a defense system in bacteria and archaea. CRISPR/Cas9 technology holds immense potential in cancer diagnosis and treatment and has been utilized to develop cancer disease models such as medulloblastoma and glioblastoma mice models. In diagnostics, CRISPR can be used to quickly and efficiently detect genes involved in various cancer development, prol

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… Cancer type | Target gene | Treated tissues and cells | Knockout status | Role | References Colorectal cancer | ERO1α | HCT116 cells | Yes | Suppress cancer development | 141 APC | HCT116 cells | Edit gene mutation | Xenograft tumor suppressor | 142 ATF3 | HCT116 and RKO Cells | Yes | Inhibit tumor invasion … and metastasis | 91 αTAT1 | HCT116 cells | Yes | Inhibit proliferation and invasion | 143 APC, P53, KRAS and SMAD4; APC and P53 | Human intestinal stem cells | Yes | Enhance tumor progression | 144 Breast cancer | miR-27b | MCF7 cells | Yes | Tumor suppressor | 145 CXCR7 and CXCR4 | MDA-MB-231 cells …

Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy.

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior.

S100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction.

The aberrant activity of Wnt signaling is an early step in the transformation of normal intestinal cells to malignant tissue, leading to more aggressive tumors, and eventually metastases. In colorectal cancer (CRC), metastasis accounts for about 90% of patient deaths, representing the most lethal event during the course of the disease and is directly linked to patient survival, critically limiting successful therapy. This review focuses on our studies of the metastasis-inducing gene S100A4, which we identified as transcriptional target of β-catenin. S100A4 increased migration and invasion in v

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… In this array we observed 40-fold increase of S100A4 expression in HCT116 cells, compared to HAB-92 wt cells. …

Implementing Curcumin in Translational Oncology Research.

Most data published on curcumin and curcumin-based formulations are very promising. In cancer research, the majority of data has been obtained in vitro. Less frequently, researchers used experimental animals. The results of several clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin in clinical oncology. However, the issues regarding timely data reporting and lack of disclosure of the exact curcumin formulations used in these studies should not be neglected. This article is a snapshot of the current status

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… Athymic mice with subcutaneous xenografs of HCT116 cells: the combination of OPCs and curcumin (both agents at 100 mg/kg) was more potent in decreasing tumor growth than the individual agents ( p = 0.0006 for tumor volume, p =0.000214 for tumor weight) [ 70 ]. …

Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis.

Although progress has been made in the treatment of cancer, particularly for the four major types of cancers affecting the lungs, colon, breast and prostate, resistance to cancer treatment often emerges upon inhibition of major signaling pathways, which leads to the activation of additional pathways as a last-resort survival mechanism by the cancer cells. This signaling plasticity provides cancer cells with a level of operational freedom, reducing treatment efficacy. Plasticity is a characteristic of cancer cells that are not only able to switch signaling pathways but also from one cellular st

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… These results were also validated in vivo, whereby LRP5-overexpressing HCT116 cells formed bigger tumors after subcutaneous injection, suggesting the importance of LRP5 in tumorigenesis. In addition, the upregulation of LRP5 induced the expression of stemness markers like OCT3/4, ALDH1A1 and CD133. … Coherently, CD133 + HCT116 cells had enhanced LRP5 mRNA levels. Interestingly, HCT116 CD133 + and HCT116 cells, in which LRP5 was upregulated, showed enhanced mRNA levels of IL6 and STAT3 . In parallel, the Wnt pathway appeared to be more active in this cell population. …

The Potential Role of Sildenafil in Cancer Management through EPR Augmentation.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for the treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 has been reported in lung, colon, metastatic breast cancers, and bladder squamous carcinoma. Moreover, sildenafil has been reported to increase the sensitivity of

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran.

Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate

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… Astragalin inhibits the proliferation and migration of human colon cancer HCT116 cells by regulating the NF-κB signaling pathway. Front. Pharmacol. 2021;12:639256. doi: 10.3389/fphar.2021.639256. 33. Tian S., Wei Y., Hu H., Zhao H. …

The role of LncRNA LBX2-AS1 in cancers: functions, mechanisms and potential clinical utility.

Increasingly advanced biology technique has revealed that long non-coding RNAs (lncRNA) as critical factors that exert significant regulatory effects on biological functions by modulating gene transcription, epigenetic modifications and protein translation. A newly emerging lncRNA, ladybird homeobox 2 (LBX2)-antisense RNA 1 (LBX2-AS1), was found to be highly expressed in various tumors. Moreover, it is functionally linked to the regulation of essential tumor-related biological processes, such as cell proliferation and apoptosis, through interactions with multiple signaling molecules/pathways.

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers.

Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present sig

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… Among these, a total of 54 DEPs (22 upregulated and 32 downregulated proteins) overlapped in DLD1 and HCT116 cells, as well as 83 DEPs (the most downregulated proteins) overlapped in Caco-2 and LOVO cells were mainly involved in specific pathways, including calcium mobilization (LAT2/NTAL/LAB), metabolism … Rhizoma extract significantly reduced the IC 50 value of fluorouracil (5-FU) in human CRC (HCT116) cells, and could act as a potential adjuvant agent against 5-FU-resistant CRCs by attenuating the expression of TS gene ( Kang et al., 2021 ). In addition, C. …