CRISPR-Based Approaches for Cancer Immunotherapy.

Clustered regularly interspaced short palindromic repeats (CRISPR) technology is a powerful gene editing tool that has the potential to revolutionize cancer treatment. It allows for precise and efficient editing of specific genes that drive cancer growth and progression. CRISPR-based approaches gene knock-out, which deletes specific genes or sequences of DNA within a cancer cell, and gene knock-in, which inserts new sequences of DNA into a cancer cell to identify potential targets for cancer therapy. Further, genome-wide CRISPR-Cas9-based screens identify specific markers for diagnosis of cancers. Recently, immunotherapy has become a highly efficient strategy for the treatment of cancer. The use of CRISPR in cancer immunotherapy is focused on enhancing the function of T cells, making them more effective at attacking cancer cells and inactivating the immune evasion mechanisms of cancer cells. It has the potential to generate CAR-T cells, which are T cells that have been genetically engineered to target and attack cancer cells specifically. This review uncovers the latest developments in CRISPR-based gene editing strategies and delivery of their components in cancer cells. In addition, the applications of CRISPR in cancer immune therapy are discussed. Overall, this review helps to explore the potential of CRISPR-based strategies in cancer immune therapy in clinical settings.

Advances in Quercetin for Drug-Resistant Cancer Therapy: Mechanisms, Applications, and Delivery Systems.

Quercetin (QUE), a natural flavone abundantly discovered in fruits, has gained attention for its potential health benefits due to its unique structure. In addition, epidemiological and clinical studies have shown promising antioxidant activity of QUE aiming to treat various diseases, including cancer. This article's purpose is to provide an overview of recent advances in the use of QUE for drug-resistant cancer therapies, focusing on its mechanisms, applications, and delivery systems. The review discusses the structure-function relationship of QUE and its role in mitigating various disorders. Furthermore, it highlights the impact of QUE on cancer and cancer stem cells, elucidating the signaling pathways at the cellular and molecular levels involved. Additionally, the review explores the mechanistic role of QUE in reversing drug resistance in different types of drug-resistant cancers. Moreover, it presents a comprehensive analysis of drug diverse delivery strategies employed for effective cancer treatment using QUE. Clinical studies investigating the safety and bioavailability of QUE are also discussed. Finally, the review concludes with future directions, emphasizing the use of cost-effective and efficient protein and peptide-based self-assembling hydrogels for targeted delivery of QUE.

Natural and Synthetic Chalcones: Potential Impact on Breast Cancer.

Chalcones are small molecules, naturally found in fruits and vegetables, and exhibit diverse pharmacological activities. They also possess anticancer activity against different tumors. They can be converted into numerous derivatives by modifying hydrogen moieties, enabling the exploration of their diverse anticancer potentials. The main aims are to provide valuable insights into the recent progress made in utilizing chalcones and their derivatives as agents against breast cancer while delivering their underlying molecular mechanisms of action. This review presents anticancer molecular mechanisms and signaling pathways modulated by chalcones. Furthermore, it helps in the understating of the precise mechanisms of action and specific molecular targets of chalcones and their synthetic derivatives for breast cancer treatment.

Gamma Delta T Cells: Role in Immunotherapy of Hepatocellular Carcinoma.

The most typical type of liver cancer or hepatocellular carcinoma (HCC) develops from hepatocyte loss. Non-alcoholic fatty liver disease (NAFLD), viral hepatitis C and cirrhosis are the leading causes of HCC. With the Hepatitis B vaccine and medicines, there are several treatments for HCC, including liver resection, ablation, transplantation, immunotherapy, gene therapy, radiation embolization, and targeted therapy. Currently, a wide range of studies are carried out on gene therapy to identify biomarkers and pathways, which help us identify the exact stage of the disorder and reduce its effects. γδT cells have recently received much interest as a potential cancer treatment method in adaptive immunotherapy. γδT cells can quickly form connections between receptor and ligand activation. They can clonally expand and are a significant source of cytokines and chemokines. The present review provides a comprehensive understanding on the function of γδT cells in immunotherapies and how they are used to treat HCC.

PM2.5: Epigenetic Alteration in Lung Physiology and Lung Cancer Pathogenesis.

Particulate matter (PM) has a very negative impact on human health, specifically the respiratory system. PM comes in many forms, among these is PM2.5,which is a major risk factor for lung cancer and other cardiovascular diseases. PM is inherent in emissions from industrial production, manufacturing, vehicle exhaust, mining, and cigarette smoking. For this reason, the composition of PM differs from area to area although its primary constituents are heavy metals and petroleum elements. PM has a long and toxic impact on human health. After extended exposure to PM2.5 the mortality rate for lung cancer patients increases. Already, lung cancer is the leading cause of death globally with the highest mortality rate. PM2.5 creates epigenetic changes in miRNA, histone modification, and DNA methylation, causing tumorigenesis followed by lung cancer.

Role of γδ T Cells in Cancer Progression and Therapy.

γδ T cells signify a foundational group of immune cells that infiltrate tumors early on, engaging in combat against cancer cells. The buildup of γδ T cells as cancer advances underscores their significance. Initially, these cells infiltrate and enact cytotoxic effects within the tumor tissue. However, in later stages, the predominant phenotype of γδ T cells undergoes changes in numerous cancers, fostering tumor growth and metastasis. Different mechanisms induced by cancer cell suppress effector action of γδ T cells and even sometimes promote cancer progression. In the early stages, stopping this mechanism clears this challenge and enables γδ T cells to effectively remove cancer cells. Given this context, it becomes imperative to delve into the mechanisms of how γδ T cells function in tumor microenvironment. This review discusses γδ T cells' role across different cancer types.

Insights into the potential of Sanguinarine as a promising therapeutic option for breast cancer.

Breast cancer (BC) is one of the leading causes of cancer-related deaths in women worldwide. The tumor microenvironment (TME) plays a crucial role in the progression and metastasis of BC. A significant proportion of BC is characterized by a hypoxic TME, which contributes to the development of drug resistance and cancer recurrence. Sanguinarine (SAN), an isoquinoline alkaloid found in Papaver plants, has shown promise as an anticancer agent. The present review focuses on exploring the molecular mechanisms of hypoxic TME in BC and the potential of SAN as a therapeutic option. The review presents the current understanding of the hypoxic TME, its signaling pathways, and its impact on the progression of BC. Additionally, the review elaborates on the mechanisms of action of SAN in BC, including its effects on vital cellular processes such as proliferation, migration, drug resistance, and tumor-induced immune suppression. The review highlights the importance of addressing hypoxic TME in treating BC and the potential of SAN as a promising therapeutic option.

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer.

HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms. In this review, we describe the regulatory mechanisms that govern HOTAIR expression during cancer development and explore how HOTAIR drives BC development, metastasis, and drug resistance. In the final section of this review, we focus on the role of HOTAIR in BC management, therapeutic treatment, and prognosis, highlighting its potential therapeutic applications.

Tumor microenvironment pathways: Cross regulation in breast cancer metastasis.

The tumor microenvironment (TME) is heterogeneous and contains a multiple cell population with surrounded immune cells, which plays a major role in regulating metastasis. The multifunctional pathways, Hedgehog (Hh), Wnt, Notch, and NF-kB, cross-regulates metastasis in breast cancer. This review presents substantial evidence for cross-regulation of TME components and signaling pathways, which makes breast TME more heterogeneous and complex, promoting breast cancer progression and metastasis as a highly aggressive form. We discoursed the importance of stromal and immune cells as well as their crosstalk in bridging the metastasis. We also discussed the role of Hh and Notch pathways in the intervention between breast cancer cells and macrophages to support TME; Notch signaling in the bidirectional communication between cancer cells and components of TME; Wnt signal pathway in controlling the factors responsible for EMT and NF-κB pathway in the regulation of genes controlling the inflammatory response. We also present the role of exosomes and their miRNAs in the cross-regulation of TME cells as well as pathways in the reprogramming of breast TME to support metastasis. Finally, we examined and discussed the targeted small molecule inhibitors and natural compounds targeting developmental pathways and proposed small molecule natural compounds as potential therapeutics of TME based on the multitargeting ability. In conclusion, the understanding of the molecular basis of the cross-regulation of TME pathways and their inhibitors helps identify molecular targets for rational drug discovery to treat breast cancers.

Regulatory T cells: Their role in triple-negative breast cancer progression and metastasis.

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. This tumorigenicity is independent of hormonal or HER2 pathways because of a lack of respective receptor expression. TNBC is extremely prone to drug resistance and early recurrence because of T-regulatory cell (Treg) infiltration into the tumor microenvironment (TME) in addition to other mechanisms like genomic instability. Tumor-infiltrating Tregs interact with both tumor and stromal cells as well as extracellular matrix components in the TME and induce an immune-suppressive phenotype. Hence, treatment of TNBC with conventional therapies remains challenging. Understanding the protective mechanism of Tregs in shielding TNBC from antitumor immune responses in the TME will pave the way for developing novel, immune-based therapeutics. The current review focuses on the role of tumor-infiltrating Tregs in tumor progression and metabolic reprogramming of the TME. The authors have extended their focus to oncotargeting Treg-mediated immune suppression in breast cancer. Because of its potential role in the TME, modulating Treg activity may provide a novel strategic intervention to combat TNBC. Both under laboratory conditions and in clinical trials, currently available anticancer drugs and natural therapeutics as potential agents for targeting Tregs are explored.

γδ T Cell-Mediated Immune Responses for Cancer Therapy: Special Focus on Breast Cancer.

Triple-negative breast cancer (TNBC) is a type of breast cancer (BC) with high aggressive nature, devoid of receptors for estrogen and progesterone hormones and with overexpression of the HER2/neu protein. It is more aggressive than other types of BC, common occurring in younger women. Recently, preclinical and clinical studies have investigated the use of immune therapies to treat TNBC patients. However, a subset of patients is responding to immunotherapy due to the high level of tumor mutation burden. The bidirectional communication among the tumor microenvironment (TME) cells via signal molecules modulates γδ T cells to support or impair tumor growth. This review emphasizes γδ T cell-mediated immune responses with a special focus on breast cancer. We present the cytotoxic characteristics of γδ T cells. We also present the promising role of γδ T cells in mounting pro-tumor and anti-tumor responses in the TME. Finally, our review focuses on prominent features of γδ T cells as a curse in breast cancer development.

Natural Chalcones and Their Derivatives Target the Tumor Microenvironment in Colon Cancer.

Chalcones are the basic chemical structural predecessors of flavonoids and isoflavonoids, frequently available in many innately arising compounds. Chalcones and their counter parts have drawn the attention of many researchers because of their extensive pharmacological activities with therapeutic potential against various clinical conditions, especially for anticancer activity. The chalcone derivatives potentially suppress the growth of tumors through multiple mechanisms, encompassing interfering cell division, control of cell degradation, triggering cell suicide, and regulating the immune response towards cancer cells and inflammatory mediators. The benefits of chalcones are consistent that researchers develop chalcone derivatives asnovel cancer therapeutic agents. Combination therapy (chalcone derivatives with other chemotherapeutic agents) is even more effective in curing colon cancer. The preclinical findings of treating cancer cells with chalone derivatives were encouraging suggesting their potential use clinically in cancer patients. However, further investigations and a complete study of the degree of toxicity associated with chalcone derivatives are required. The current review summarizes the pharmacological and immunological properties of chalcones and their anticancer activities with their possible mechanisms of action in colon cancer.

Contemporary clinical trials in pancreatic cancer immunotherapy targeting PD-1 and PD-L1.

Pancreatic cancer (PC) is a major gastrointestinal cancer in terms of worldwide incidence and mortality. Despite advances in diagnostic and treatment modalities, the mortality of PC is still a serious concern in both sexes. Immune therapy using inhibitors of immune checkpoints, especially inhibitors of programmed cell death protein 1/programmed cell death ligand-1(PD-1/PD-L1), offer huge benefits to cancer patients. This review describes an up-to-date information on the role of PD-1 and PD-L1 in the development of immune tolerance in PC alongside the current clinical trials and the known outcomes citing the available literature. We also included the details on PD-1/PD-L1-mediated signalling in maintenance of PC stem cells and metastasis. We reviewed the critical information on safety, tolerance, and efficacy of clinically important regimens of PD-1/PD-L1 blocking agents and targeted therapeutics. This review elucidates the underlying mechanisms of PD-1/PD-L1 alliance in tolerance of the immune system, maintenance of stem cells, and metastasis promotion as well as design regimens with high safety and excellent tolerability and efficacy for management of PC in advanced stages.

Natural products: Potential targets of TME related long non-coding RNAs in lung cancer.

BACKGROUND: Lung cancer is a significant health concern worldwide due to high mortality and morbidity, despite the advances in diagnosis, treatment, and management. Recent experimental evidence from different models suggested long non-coding RNAs (lncRNAs) as major modulators of cancer stem cells (CSCs) in the tumor microenvironment (TME) to support metastasis and drug resistance in lung cancer. Evidence-based studies demonstrated that natural products interfere with TME functions. PURPOSE OF STUDY: To establish lncRNAs of TME as novel targets of natural compounds for lung cancer management. STUDY DESIGN: Current study used a combination of TME and lung CSCs, lncRNAs and enrichment and stemness maintenance, natural products and stem cell management, natural products and lncRNAs, natural products and targeted delivery as keywords to retrieve the literature from Scopus, Web of Science, PubMed, and Google Scholar. This study critically reviewed the current literature and presented cancer stem cells' ability in reprogramming lung TME. RESULTS: This review found that TME related oncogenic and tumor suppressor lncRNAs and their signaling pathways control the maintenance of stemness in lung TME. This review explored natural phenolic compounds and found that curcumin, genistein, quercetin epigallocatechin gallate and ginsenoside Rh2 are efficient in managing lung CSCs. They modulate lncRNAs and their upstream mediators by targeting signaling and epigenetic pathways. This review also identified relevant nanotechnology-based phytochemical delivery approaches for targeting lung cancer. CONCLUSION: By critical literature analysis, TME related lncRNAs were identified as potential therapeutic targets, aiming to develop natural product-based therapeutics to treat metastatic and drug-resistant lung cancers.

Understanding the function of the tumor microenvironment, and compounds from marine organisms for breast cancer therapy.

The pathology and physiology of breast cancer (BC), including metastasis, and drug resistance, is driven by multiple signaling pathways in the tumor microenvironment (TME), which hamper antitumor immunity. Recently, long non-coding RNAs have been reported to mediate pathophysiological develop-ments such as metastasis as well as immune suppression within the TME. Given the complex biology of BC, novel personalized therapeutic strategies that address its diverse pathophysiologies are needed to improve clinical outcomes. In this review, we describe the advances in the biology of breast neoplasia, including cellular and molecular biology, heterogeneity, and TME. We review the role of novel molecules such as long non-coding RNAs in the pathophysiology of BC. Finally, we provide an up-to-date overview of anticancer compounds extracted from marine microorganisms, crustaceans, and fishes and their synergistic effects in combination with other anticancer drugs. Marine compounds are a new discipline of research in BC and offer a wide range of anti-cancer effects that could be harnessed to target the various pathways involved in BC development, thus assisting current therapeutic regimens.

Long Noncoding RNAs: Potential Mediators of Liver Cancer Metastasis.

Liver cancer (LC) is the most common high-mortality malignancy, due to its aggressive nature, heterogeneity, and metastasis. Recent studies have recognized long noncoding RNAs (lncRNAs) as mediators of LC pathogenesis and metastasis. This review describes the role of lncRNAs in molecular mechanisms of tumorigenicity, metastasis, stem-cell maintenance, drug resistance, and tumor immunity. We present recent updates on therapeutic targeting of lncRNAs in LC as well as lncRNA's potential for LC diagnosis. Overall, we provide a new perspective on the role of lncRNAs for LC treatment and diagnosis.

Exosomes: Critical Mediators of Tumour Microenvironment Reprogramming.

Tumour microenvironment (TME) is a resident of a variety of cells, which are devoted to the heterogeneous population of the tumour. TME establishes a communication network for crosstalk and signalling between tumour cells, stroma, and other interstitial cells. The cross-communication drives the reprogramming of TME cells, which promote cancer progression and metastasis via diverse signalling pathways. Recently, TMEderived exosomes are recognized as critical communicators of TME cell reprogramming. This review addresses the role of TME-derived exosomes in the modulation of stroma, including reprogramming the stromal cells, ECM and tumour cell metabolism, as well as neoplastic transformation. Subsequently, we described the role of exosomes in pre-metastatic niche development, maintenance of stemness and tumour vasculature, as well as development of drug resistance. We also explored tumour-derived exosomes in precision, including diagnosis, drug delivery, and vaccine development. We discussed the currently established bioengineered exosomes as carriers for chemotherapeutic drugs, RNAi molecules, and natural compounds. Finally, we presented tetraspanin and DNA-based precision methods for the quantification of tumour-derived exosomes. Overall, TMEderived exosome-mediated reprogramming of TME and precision strategies could illuminate the potential mechanisms for targeted therapeutic intervention.

Horizons of nanotechnology applications in female specific cancers.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.