Cancer Therapeutic Applications Research Articles

Identification of Potent CHK2 Inhibitors‐Modulators for Therapeutic Application in Cancer: A Machine Learning Integrated Fragment‐Based Drug Design Approach

AbstractThe CHK2 protein regulates the cell division cycle and responds to DNA damage. Additionally, it facilitates the repair of DNA damage and maintains the integrity of its biological processes. Dysregulation of the CHK2 protein is associated with a predisposition to harmful diseases. The current research protocol was designed to identify novel hit molecules as CHK2 inhibitors and disrupt the normal biological function of the CHK2 protein via a fragment‐based drug discovery approach. The protocol involved generating fragments using the MacFrag tool, followed by a chemical similarity search utilizing RDKit to identify fragment molecules analogous to previously established CHK2 inhibitor scaffolds. The bioactive molecules were constructed using the Fragmenstein tool, followed by molecular docking simulations to investigate their binding affinity. In addition, pharmacokinetic properties were analyzed, and a molecular dynamics simulation study was conducted to assess the stability of selected compounds with CHK2 protein. Finally, five novel compounds were identified as excellent CHK2 inhibitors through the FBDD and show good binding interactions at active sites of CHK2 with beneficial ADMET properties. This research work presents novel CHK2 inhibitor molecules that have the potential to be utilized in drug discovery, serving as key leads for future advancements in healthcare industries and sectors.

Current scenario of pyrazole hybrids with anti-breast cancer therapeutic applications.

Breast cancer stands as the leading cause of cancer-related deaths among women globally, but current therapy is restricted to the serious adverse effects and multidrug resistance, necessitating the exploration of novel, safe, and efficient anti-breast cancer chemotherapeutic agents. Pyrazoles exhibit excellent potential for utilization as effective anti-breast cancer agents due to their ability to act on various biological targets. Particularly, pyrazole hybrids demonstrated the advantage of targeting multiple pathways, and some of them, which are exemplified by larotrectinib (pyrazolo[1,5-a]pyrimidine hybrid), can be applied for breast cancer therapy. Thus, pyrazole hybrids hold great promise as useful therapeutic interventions for breast cancer. The aim of this review is to summarize the current scenario of pyrazole hybrids with in vitro and/or in vivo anti-breast cancer potential, along with the modes of action and structure-activity relationships, covering articles published from 2020 to the present, to streamline the development of rational, effective and safe anti-breast cancer candidates.

Comprehensive analysis of the potential biological significance of CCL5 in pan-cancer prognosis and immunotherapy

C-C chemokine ligand 5 (CCL5) plays a crucial role in the advancement of human cancer. Nevertheless, little is known about the multi-omics characterisation of CCL5 and its significance for the immune microenvironment and prognosis of tumor patients. The basal expression levels of the CCL5 gene in normal human tissues, aberrant expression in disease, genomic alterations, prognostic roles, pathway enrichment, immune microenvironment, association with immune checkpoints, drug sensitivity, and the ability to predict patients’ immunotherapeutic response to immune checkpoint inhibitors (ICIs) and small molecule drugs were all thoroughly analyzed using data gathered from 33 cancers. Lastly, we were able to validate CCL5’s involvement in renal clear cell carcinoma by experimental means. We discovered that CCL5 has distinct expression patterns and a diagnostic biomarker significance in cancer. Furthermore, we discovered that CCL5 is essential for both the tumor microenvironment and pan-cancer. TMB and MSI are two frequent immunological checkpoints that are significantly correlated with CCL5, and patients who express high levels of CCL5 have stronger immunotherapeutic response and a better prognosis after immunotherapy. Eventually, molecular docking was used to find small molecule inhibitors that can specifically target CCL5. Ultimately, it was shown that CCL5 knockdown impeded renal clear cell carcinoma cells’ ability to proliferate and invade. Our findings demonstrate the significant potential of CCL5 as an immunotherapeutic response biomarker and prognostic indicator, which may pave the way for more studies on the mechanism of tumor infiltration and CCL5’s potential therapeutic applications in cancer.

Exosomes: from basic research to clinical diagnostic and therapeutic applications in cancer

Exosomes: from basic research to clinical diagnostic and therapeutic applications in cancer

Encapsulation of Inositol Hexakisphosphate with Chitosan via Gelation to Facilitate Cellular Delivery and Programmed Cell Death in Human Breast Cancer Cells.

Inositol hexakisphosphate (InsP6) is the most abundant inositol polyphosphate both in plant and animal cells. Exogenous InsP6 is known to inhibit cell proliferation and induce apoptosis in cancerous cells. However, cellular entry of exogenous InsP6 is hindered due to the presence of highly negative charge on this molecule. Therefore, to enhance the cellular delivery of InsP6 in cancerous cells, InsP6 was encapsulated by chitosan (CS), a natural polysaccharide, via the ionic gelation method. Our hypothesis is that encapsulated InsP6 will enter the cell more efficiently to trigger its apoptotic effects. The incorporation of InsP6 into CS was optimized by varying the ratios of the two and confirmed by InsP6 analysis via polyacrylamide gel electrophoresis (PAGE) and atomic absorption spectrophotometry (AAS). The complex was further characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) for physicochemical changes. The data indicated morphological changes and changes in the spectral properties of the complex upon encapsulation. The encapsulated InsP6 enters human breast cancer MCF-7 cells more efficiently than free InsP6 and triggers apoptosis via a mechanism involving the production of reactive oxygen species (ROS). This work has potential for developing cancer therapeutic applications utilizing natural compounds that are likely to overcome the severe toxic effects associated with synthetic chemotherapeutic drugs.

Advances in spatial multi-omics in tumors.

Single-cell techniques have convincingly demonstrated that tumor tissue usually contains multiple genetically defined cell subclones with different gene mutation sets as well as various transcriptional profiles, but the spatial heterogeneity of the microenvironment and the macrobiological characteristics of the tumor ecosystem have not been described. For the past few years, spatial multi-omics technologies have revealed the cellular interactions, microenvironment, and even systemic tumor-host interactions in the tumor ecosystem at the spatial level, which can not only improve classical therapies such as surgery, radiotherapy, and chemotherapy but also promote the development of emerging targeted therapies in immunotherapy. Here, we review some emerging spatial omics techniques in cancer research and therapeutic applications and propose prospects for their future development.

Cancer-Targeting and Viscosity-Activatable Near-Infrared Fluorescent Probe for Precise Cancer Cell Imaging.

Small-molecule fluorescent probes have emerged as potential tools for cancer cell imaging-based diagnostic and therapeutic applications, but their limited selectivity and poor imaging contrast hinder their broad applications. To address these problems, we present the design and construction of a novel near-infrared (NIR) biotin-conjugated and viscosity-activatable fluorescent probe, named as QL-VB, for selective recognition and imaging of cancer cells. The designed probe exhibited a NIR emission at 680 nm, with a substantial Stokes shift of 100 nm and remarkably sensitive responses toward viscosity changes in solution. Importantly, QL-VB provided an evidently enhanced signal-to-noise ratio (SNR: 6.2) for the discrimination of cancer cells/normal cells, as compared with the control probe without biotin conjugation (SNR: 1.8). Moreover, we validated the capability of QL-VB for dynamic monitoring of stimulated viscosity changes within cancer cells and employed QL-VB for distinguishing breast cancer tissues from normal tissues in live mice with improved accuracy (SNR: 2.5) in comparison with the control probe (SNR: 1.8). All these findings indicated that the cancer-targeting and viscosity-activatable NIR fluorescent probe not only enables the mechanistic investigations of mitochondrial viscosity alterations within cancer cells but also holds the potential as a robust tool for cancer cell imaging-based applications.

Unveiling the therapeutic potential of epigallocatechin gallate in liver cancer: insights from network pharmacology and in vitro assays

Epigallocatechin gallate (EGCG) is a prominent catechin found in green tea polyphenols and has shown promising anti-tumor properties. However, the exact regulatory mechanism of EGCG on liver cancer is not fully revealed. In this study, we conducted integrative analyses using the SwissTargetPrediction and GeneCards repositories, which identified 98 targets. These targets were used to construct a protein-protein interaction network using STRING and visualised with Cytoscape. Central to this network are hub proteins, notably TNF and PIK3CA, suggesting pivotal roles in the therapeutic landscape. Gene Ontology (GO) enrichment analysis unveiled 1,570 biological terms with a notable preponderance within oxidative stress response processes. Complementary pathway enrichment via the Kyoto Encyclopaedia of Genes and Genomes (KEGG) highlighted 134 pathways, with the PI3K-Akt pathway emerging as prominent. In silico molecular docking supported these findings, revealing binding energies of EGCG-target complexes below −7.0 kcal/mol, indicative of robust interactions. Moreover, cellular assays including CCK-8, wound-healing, and Transwell modalities, established EGCG’s inhibitory concentration-dependent effects on HepG2 cell proliferation, migration, and invasion. Apoptotic assays affirmed by FACS, evidenced enhanced apoptosis with escalating EGCG concentrations, underpinned by modulations in caspase activity and apoptotic protein levels. Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.

The current landscape of coumarin hybrids with antibreast cancer therapeutic applications: An updated review.

Globally, breast cancer (BC) has the highest prevalence among malignant diseases. BC is also the primary cause of death among women. Notably, BC morbidity has been increasing continuously at an approximate growth rate of 2.2% per year. Persistent BC is a major public health issue worldwide. Consequently, novel chemotherapeutic agents to combat this lethal disease should be developed urgently. Coumarins with interesting structural and mechanistic variations exhibit promising activity in several forms of BC, including BCs with multidrug resistance. In particular, coumarin hybrids composed of coumarin and one or more anti-BC pharmacophores can target different biological components in BC cells simultaneously. Thus, coumarin hybrids are useful scaffolds that can help improve the anti-BC efficacy of coumarins, reduce side effects, improve pharmacokinetics, minimize drug-drug interactions, and circumvent drug resistance. This review, in which articles published from 2020 to the present day have been evaluated, highlights the landscape of coumarin hybrids that exhibit therapeutic effects against breast cancer. These findings can aid further investigations on novel antibreast-cancer therapeutics.

Phytochemical Targeting of Nerve Growth Factor by Thymoquinone and Cuscutin: A Molecular Dynamics Simulation Study.

Background Nerve growth factor (NGF) is a novel target of pain therapeutics for oral cancer, and it plays a main role in the nociception of chronic pain. Surgery, along with chemotherapy or radiotherapy, is the gold standard for treating patients, but the side effects are significant as well. Newer effective interventions with natural phytochemicals could improve patient compliance and enhance the quality of life among patients with oral cancer. A literature search revealed a positive correlation between NGF and oral cancer pain. Nigella sativa (N. sativa) and Cuscuta reflexa (C. reflexa) have proven anticancer effects, but their activity with NGF is unexplored. Aims and objectives We aimed to identify the potential phytochemicals in N. sativa and C. reflexa. We also checked the NGF-blocking activity of the phytochemicals. Molecular docking and molecular dynamic (MD) simulations evaluated the binding energy and stability between the NGF protein and selected phytochemical ligands. Materials and methods We obtained protein NGF structure from UniProt (ID: 4EDX, P01138, Beta-nerve growth factor), ligand (thymoquinone) structure using PubChem ID: 10281, and ligand (cuscutin) structure using PubChem ID: 66065. Maestro protein (Schrödinger Inc., Mannheim, Germany) was used for molecular docking. Desmond Simulation Package (Schrödinger Inc., Mannheim, Germany) was used to model MDfor 100 nanoseconds (ns). We have assessed the interaction between the protein and ligands by root mean square deviation (RMSD) values. Results The interaction of thymoquinone and cuscutin with NGF was assessed. While interacting with thymoquinone, there was mild fluctuation from 0.6 Å to 2.5 Å up to 80 ns and ended up at 4.8 Å up to 100 ns. While interacting with cuscutin, mild fluctuation was seen from 0.8 Å to 4.8 Å till 90 ns and ended at 6.4 Å up to 100 ns. We found a stable interaction between our drug combination and the NGF receptor. Conclusion We have identified a stable interaction between thymoquinone, cuscutin, and NGF by our MD simulations. Hence, it could be used as an NGF inhibitor for pain relief and to control tumor progression. Further in vitro and in vivo evaluations of this novel drug combination with phytochemicals will help us understand their biological activities and potential clinical applications in oral cancer therapeutics.

Ultrasmall Carbon Nanodots as Theranostic Nanoheaters for Precision Breast Cancer Phototherapy: Establishing the Translational Potential in Tumor-in-a-Dish Models.

This study investigates the remarkable attributes of sulfur-doped carbon nanodots (CDs) synthesized in high yield and a narrow size distribution (4.8 nm). These CDs exhibit notable features, including potential bioelimination through renal clearance and efficient photothermal conversion in the near-infrared region with multicolor photoluminescence across the visible spectrum. Our research demonstrates high biocompatibility and effective near-infrared (NIR)-triggered photothermal toxicity when targeting mammospheres and patient-derived tumor organoids. Moreover, the study delves into the intricate cellular responses induced by CD-mediated hyperthermia. This involves efficient tumor mass death, activation of the p38-mitogen-activated protein kinase (MAPK) pathway, and upregulation of genes associated with apoptosis, hypoxia, and autophagy. The interaction of CDs with mammospheres reveals their ability to penetrate the complex microenvironment, impeded at 4 °C, indicating an energy-dependent endocytosis mechanism. This observation underscores the CDs' potential for targeted drug delivery, particularly in anticancer therapeutics. This investigation contributes to understanding the multifunctional properties of sulfur-doped CDs and highlights their promising applications in cancer therapeutics. Utilizing 3-D tumor-in-a-dish patients' organoids enhances translational potential, providing a clinically relevant platform for assessing therapeutic efficacy in a context mirroring the physiological conditions of cancerous tissues.

Novel selective inhibitors of macropinocytosis-dependent growth in pancreatic ductal carcinoma

Macropinocytosis is a cellular process that enables cells to engulf extracellular material, such as nutrients, growth factors, and even whole cells. It is involved in several physiological functions as well as pathological conditions. In cancer cells, macropinocytosis plays a crucial role in promoting tumor growth and survival under nutrient-limited conditions. In particular KRAS mutations have been identified as main drivers of macropinocytosis in pancreatic, breast, and non-small cell lung cancers. We performed a high-content screening to identify inhibitors of macropinocytosis in pancreatic ductal adenocarcinoma (PDAC)-derived cells, aiming to prevent nutrient scavenging of PDAC tumors. The screening campaign was conducted in a well-known pancreatic KRAS-mutated cell line (MIAPaCa-2) cultured under nutrient deprivation and using FITC-dextran to precisely quantify macropinocytosis. We assembled a collection of 3584 small molecules, including drugs approved by the Food and Drug Administration (FDA), drug-like molecules against molecular targets, kinase-targeted compounds, and molecules designed to hamper protein-protein interactions. We identified 28 molecules that inhibited macropinocytosis, with potency ranging from 0.4 to 29.9 μM (EC50). A few of them interfered with other endocytic pathways, while 11 compounds did not and were therefore considered specific “bona fide” macropinocytosis inhibitors and further characterized. Four compounds (Ivermectin, Tyrphostin A9, LY2090314, and Pyrvinium Pamoate) selectively hampered nutrient scavenging in KRAS-mutated cancer cells. Their ability to impair albumin-dependent proliferation was replicated both in different 2D cell culture systems and 3D organotypic models.These findings provide a new set of compounds specifically targeting macropinocytosis, which could have therapeutic applications in cancer and infectious diseases.

Ramifications of m6A Modification on ncRNAs in Cancer.

N6-methyladenosine (m6A) is an RNA modification wherein the N6-position of adenosine is methylated. It is one of the most prevalent internal modifications of RNA and regulates various aspects of RNA metabolism. M6A is deposited by m6A methyltransferases, removed by m6A demethylases, and recognized by reader proteins, which modulate splicing, export, translation, and stability of the modified mRNA. Recent evidence suggests that various classes of non- coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long con-coding RNAs (lncRNAs), are also targeted by this modification. Depending on the ncRNA species, m6A may affect the processing, stability, or localization of these molecules. The m6A- modified ncRNAs are implicated in a number of diseases, including cancer. In this review, the author summarizes the role of m6A modification in the regulation and functions of ncRNAs in tumor development. Moreover, the potential applications in cancer prognosis and therapeutics are discussed.

Current Expansion of Silver and Gold Nanomaterials towards Cancer Theranostics: Development of Therapeutics

Abstract: Nanomaterial-based therapeutics is an emerging tool for the treatment of numerous types of cancer. Various types of polymeric, lipid and inorganic nanoparticles (NPs) result in a wider series of applications in cancer diagnosis and therapeutics. The NPs properties are due to high surface area to volume ratio, surface plasmon resonance, absorption in the visible spectrum and light scattering. These unique characteristics of NPs arise due to their optical surface properties for conjugation/surface modification and smaller size. In cancer therapeutics, NPs based products are used as a biomarker for early detection/diagnosis of tumours, drug nano-conjugates for the delivery of chemotherapeutic drugs to the tumour-specific site, chemo-protective agents, etc. : Furthermore, other advantages of NPs are biocompatibility, lesser toxicity, enhanced permeability and retention effect, higher stability, and specific targeting with a selective accumulation of nano drugs in the tissue of the tumour. The selective targeting of NPs to tumour tissue is possible by adding surface-active targeting agents i.e., antibodies. The selective transport of drug NPs conjugates to the cancer cells is increased and extravagated due to permeable vasculature from endothelial cells gap while failing the transport of drug NPs conjugates in normal cells. This review emphasizes metallic NPs, including silver NPs (AgNPs) and gold NPs (AuNPs), which are extensively reconnoitered in various applications in cellular targeting, imaging, drug delivery, DNA-NPs conjugates for biosensor/point of care devices development, photothermal/photodynamic therapy, protein-protein interaction, etc. In addition, this review discussed different synthetic methods of AgNPs and AuNPs and characterization methods. Furthermore, it highlighted the different properties and applications of AgNPs and AuNPs in cancer theranostics.

Current Scenario of Sulfonamide Hybrids with Anti-Breast Cancer Therapeutic Applications: I. Sulfonamide-Five-Membered Heterocycle Hybrids

Current Scenario of Sulfonamide Hybrids with Anti-Breast Cancer Therapeutic Applications: I. Sulfonamide-Five-Membered Heterocycle Hybrids

Water-Soluble Small Organic Fluorophores for Oncological Theragnostic Applications: Progress and Development.

Cancer is one of the major noncommunicable diseases, responsible for millions of deaths every year worldwide. Though various cancer detection and treatment modalities are available today, many deaths occur owing to its late-stage detection and metastatic nature. Noninvasive detection using luminescence-based imaging tools is considered one of the promising techniques owing to its low cost, high sensitivity, and brightness. Moreover, these tools are unique and valuable as they can detect even the slightest changes in the cellular microenvironment. To achieve this, a fluorescent probe with strong tumor uptake and high spatial and temporal resolution, especially with highwatersolubility, is highly demanded. Recently, several water-soluble molecules with emission windows in the visible (400-700nm), first near-infrared (NIR-I, 700-1000nm), and second near-infrared (NIR-II, 1000-1700nm) windows have been reported in literature. This review highlights recently reported water-soluble small organic fluorophores/dyes with applications in cancer diagnosis and therapeutics. We systematically highlight and describe the key concepts, structural classes of fluorophores, strategies for imparting water solubility, and applications in cancer therapy and diagnosis, i.e., theragnostics. We discuss examples of water-soluble fluorescent probes based on coumarin, xanthene, boron-dipyrromethene (BODIPY), and cyanine cores. Some other emerging classes of dyes based on carbocyclic and heterocyclic cores are also discussed. Besides, emerging molecular engineering methods to obtain such fluorophores are discussed. Finally, the opportunities and challenges in this research area are also delineated.

Terminalia bellirica (Gaertn.) Roxb. extract-mediated green synthesis of magnesium oxide nanoparticles for multifunctional applications

Green synthesis has emerged as a pivotal facet of nanotechnology, garnering significant attention for its inherent safety and eco-friendly attributes. This study presents a novel approach utilizing phytochemicals derived from Terminalia bellirica (Gaertn.) Roxb. fruit extract for the environmentally benign synthesis of magnesium oxide (MgO) nanoparticles. The resultant MgO nanoparticles were comprehensively characterized using UV–visible spectroscopy, X-ray Diffractometer (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Energy dispersive X-ray (EDX), and High-Resolution-Transmission Electron Microscope (HR-TEM). The synthesized MgO nanoparticles exhibited remarkable stability, evidenced by zeta potential of −8.84 mV and an average size of 73.41 nm. In an eco-physiological context, the application of MgO nanoparticles at a concentration of 5 mg/100 ml significantly enhanced shoot length (7.94±0.70 cm), root length (8.44±0.53 cm), moisture content (97.16±0.83%), and chlorophyll expression (18.34±0.99 mg/g fresh weight (FW)) in Trigonella foenum-graecum seedlings. Furthermore, the MgO nanoparticles demonstrated biocompatibility with soil bacteria and exhibited potent photocatalytic activity, achieving a 42% degradation efficiency of the organic dye methyl orange under UV irradiation for 60 minutes. In the realm of biomedical applications, MgO nanoparticles displayed dose-dependent cytotoxicity against human breast cancer cells (MCF-7), with an IC50 value of 37.39±0.05 µg/ml. Remarkably, MgO nanoparticles were also harnessed for their memcapacitive properties, showcasing excellent non-volatile memory characteristics, including endurance for 15,000 cycles and retention for 4000 seconds. In summary, this study underscores the multifunctional prowess of MgO nanoparticles synthesized through Terminalia bellirica fruit extract, spanning applications in plant physiology, environmental remediation, cancer therapeutics, and nanoelectronics. The environmentally conscious synthesis approach and diverse functionalities presented herein position these nanoparticles as future promising candidates for sustainable and versatile technological advancements.

In vitro anticancer activity of Hirudinaria manillensis methanolic extract and its validation using in silico molecular docking approach.

Cancer has emerged as a potentially lethal illness, which recently upsurged in the mortality rate. Animal-derived compounds could be promising targets with higher efficacy and low toxicity in anticancer therapy. The present study aimed to explore the presence of anticancer potential compounds in Hirudinaria manillensis methanolic extract and their anticancer potential against various cancer cell types and target identification by Auto dock method. Initially, the identification of bioactive compounds was achieved by GC-MS analysis followed by the anticancer activity by MTT assay against A549, HeLa, MDA-MB-231, MG-63, and MOLT-4. Further, the effect of a lead compound on the cancer cell target was analyzed by the Auto dock method. GC-MS analysis results revealed the presence of 25 different bioactive compounds including anticancer potential compounds, such as Lupeol, Carvacrol, and Demecolcine. Interestingly, MTT assay results demonstrated the anticancer potential of Hirudinaria manillensis extract (LE) against various cancer cell lines, such as A549 (54.60µg/ml), HeLa (19.93µg/ml), MDA-MB-231 (20.23µg/ml), MG-63 (20.04µg/ml), and MOLT-4 (171.8µg/ml), respectively. Among these cell types, the maximum inhibition was observed against HeLa with the IC50 concentration of 19.93µg/ml. Furthermore, Demecolcine compound was docked with the EGFR tyrosine kinase showed the binding affinity of the docked complex was predicted to be - 6.2kcal/mol. Thus, we conclude that H. manillensis has a significant anticancer effect on human cancer cell lines and could be used as a natural target which paves the way for further studies on biomedical applications in cancer therapeutics.

Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications.

Adaptor proteins play essential roles in various intracellular signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that possesses pleckstrin homology (PH) and Src homology 2 (SH2) domains, as well as a YXXQ signal transducer and activator of transcription 3 (STAT3)-binding motif in its C-terminal region. STAP-2 is also a substrate of breast tumor kinase (BRK). STAP-2/BRK expression is deregulated in breast cancers and enhances STAT3-dependent cell proliferation. In prostate cancer cells, STAP-2 interacts with and stabilizes epidermal growth factor receptor (EGFR) after stimulation, resulting in the upregulation of EGFR signaling, which contributes to cancer-cell proliferation and tumor progression. Therefore, inhibition of the interaction between STAP-2 and BRK/EGFR may be a possible therapeutic strategy for these cancers. For this purpose, peptides that interfere with STAP-2/BRK/EGFR binding may have great potential. Indeed, the identified peptide inhibitor successfully suppressed the STAP-2/EGFR protein interaction, EGFR stabilization, and cancer-cell growth. Furthermore, the peptide inhibitor suppressed tumor formation in human prostate- and lung-cancer cell lines in a murine xenograft model. This review focuses on the inhibitory peptide as a promising candidate for the treatment of prostate and lung cancers.

Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.

Recent advances have brought forth the complex interplay between tumor cell plasticity and its consequential impact on drug resistance and tumor recurrence, both of which are critical determinants of neoplastic progression and therapeutic efficacy. Various forms of tumor cell plasticity, instrumental in facilitating neoplastic cells to develop drug resistance, include epithelial-mesenchymal transition (EMT) alternatively termed epithelial-mesenchymal plasticity, the acquisition of cancer stem cell (CSC) attributes, and transdifferentiation into diverse cell lineages. Nuclear receptors (NRs) are a superfamily of transcription factors (TFs) that play an essential role in regulating a multitude of cellular processes, including cell proliferation,differentiation, and apoptosis. NRs have been implicated to play a critical role in modulating gene expression associated with tumor cell plasticity and drug resistance. This review aims to provide a comprehensive overview of the current understanding of how NRs regulate these key aspects of cancer biology. We discuss the diverse mechanisms through which NRs influence tumor cell plasticity, including EMT, stemness, and metastasis. Further, we explore the intricate relationship between NRs and drug resistance, highlighting the impact of NR signaling on chemotherapy, radiotherapy andtargeted therapies. We also discuss the emerging therapeutic strategies targeting NRs to overcome tumor cell plasticity and drug resistance. This review also provides valuable insights into the current clinical trials that involve agonists or antagonists of NRs modulating various aspects of tumor cell plasticity, thereby delineating the potential of NRs as therapeutic targets for improved cancer treatment outcomes.