The emerging role of human papillomavirus in lung cancer.

Lung cancer stands as one of the most lethal diseases and is the foremost cause of cancer-related mortalities worldwide. The pathophysiology of lung cancer is multifaceted, and it includes multiple cell signaling pathways and other complex factors such as oxidative stress and genetics. The association of HPV with lung carcinogenesis was first proposed in 1979, and since then, scientists worldwide have been putting forward several hypotheses to establish a relationship between this virus and lung cancer. Although studies have reported the presence of HPV in lung cancer, the exact mechanism of entry and the route of transmission have not been elucidated clearly till now. Numerous studies across the globe have detected differentially expressed HPV oncoproteins in lung cancer patients and found their association with the critical cell signaling pathways that leads to the development and progression of lung cancer. Many reports have also provided evidence stating the involvement of HPV in determining the survival status of lung cancer patients. The present review recapitulates the studies evincing the association of HPV and lung cancer, its route of transmission and mechanism of action; the detection of the virus and treatment opportunities for HPV-positive lung cancer; and the severity associated with this disease. Therefore, this will provide an explicit idea and would help to develop preventive measures and specific as well as effective treatment for HPV-associated lung carcinogenesis.

Natural compounds targeting YAP/TAZ axis in cancer: Current state of art and challenges.

Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target cancer.

Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far?

Metabolic reprogramming, a hallmark of cancer, allows cancer cells to adapt to their specific energy needs. The Warburg effect benefits cancer cells in both hypoxic and normoxic conditions and is a well-studied reprogramming of metabolism in cancer. Interestingly, the alteration of other metabolic pathways, especially lipid metabolism has also grabbed the attention of scientists worldwide. Lipids, primarily consisting of fatty acids, phospholipids and cholesterol, play essential roles as structural component of cell membrane, signalling molecule and energy reserves. This reprogramming primarily involves aberrations in the uptake, synthesis and breakdown of lipids, thereby contributing to the survival, proliferation, invasion, migration and metastasis of cancer cells. The development of resistance to the existing treatment modalities poses a major challenge in the field of cancer therapy. Also, the plasticity of tumor cells was reported to be a contributing factor for the development of resistance. A number of studies implicated that dysregulated lipid metabolism contributes to tumor cell plasticity and associated drug resistance. Therefore, it is important to understand the intricate reprogramming of lipid metabolism in cancer cells. In this review, we mainly focused on the implication of disturbed lipid metabolic events on inducing tumor cell plasticity-mediated drug resistance. In addition, we also discussed the concept of lipid peroxidation and its crucial role in phenotypic switching and resistance to ferroptosis in cancer cells. Elucidating the relationship between lipid metabolism, tumor cell plasticity and emergence of resistance will open new opportunities to develop innovative strategies and combinatorial approaches for the treatment of cancer.

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 and targeted 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.

Exploring the nexus of nuclear receptors in hematological malignancies.

Hematological malignancies (HM) represent a subset of neoplasms affecting the blood, bone marrow, and lymphatic systems, categorized primarily into leukemia, lymphoma, and multiple myeloma. Their prognosis varies considerably, with a frequent risk of relapse despite ongoing treatments. While contemporary therapeutic strategies have extended overall patient survival, they do not offer cures for advanced stages and often lead to challenges such as acquisition of drug resistance, recurrence, and severe side effects. The need for innovative therapeutic targets is vital to elevate both survival rates and patients' quality of life. Recent research has pivoted towards nuclear receptors (NRs) due to their role in modulating tumor cell characteristics including uncontrolled proliferation, differentiation, apoptosis evasion, invasion and migration. Existing evidence emphasizes NRs' critical role in HM. The regulation of NR expression through agonists, antagonists, or selective modulators, contingent upon their levels, offers promising clinical implications in HM management. Moreover, several anticancer agents targeting NRs have been approved by the Food and Drug Administration (FDA). This review highlights the integral function of NRs in HM's pathophysiology and the potential benefits of therapeutically targeting these receptors, suggesting a prospective avenue for more efficient therapeutic interventions against HM.

Crosstalk between Non-Coding RNAs and Wnt/ß-Catenin Signaling in Head and Neck Cancer: Identification of Novel Biomarkers and Therapeutic Agents.

Head and neck cancers (HNC) encompass a broad spectrum of neoplastic disorders characterized by significant morbidity and mortality. While contemporary therapeutic interventions offer promise, challenges persist due to tumor recurrence and metastasis. Central to HNC pathogenesis is the aberration in numerous signaling cascades. Prominently, the Wnt signaling pathway has been critically implicated in the etiology of HNC, as supported by a plethora of research. Equally important, variations in the expression of non-coding RNAs (ncRNAs) have been identified to modulate key cancer phenotypes such as cellular proliferation, epithelial-mesenchymal transition, metastatic potential, recurrence, and treatment resistance. This review aims to provide an exhaustive insight into the multifaceted influence of ncRNAs on HNC, with specific emphasis on their interactions with the Wnt/ß-catenin (WBC) signaling axis. We further delineate the effect of ncRNAs in either exacerbating or attenuating HNC progression via interference with WBC signaling. An overview of the mechanisms underlying the interplay between ncRNAs and WBC signaling is also presented. In addition, we described the potential of various ncRNAs in enhancing the efficacy of chemotherapeutic and radiotherapeutic modalities. In summary, this assessment posits the potential of ncRNAs as therapeutic agents targeting the WBC signaling pathway in HNC management.

Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?

Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contribute to curcumin's limited oral bioavailability. In order to improve its oral bioavailability, different formulation techniques such as coadministration with piperine, incorporation into micelles, micro/nanoemulsions, nanoparticles, liposomes, solid dispersions, spray drying, and noncovalent complex formation with galactomannosides have been investigated with in vitro cell culture models, in vivo animal models, and humans. In the current study, we extensively reviewed clinical trials on various generations of curcumin formulations and their safety and efficacy in the treatment of many diseases. We also summarized the dose, duration, and mechanism of action of these formulations. We have also critically reviewed the advantages and limitations of each of these formulations compared to various placebo and/or available standard care therapies for these ailments. The highlighted integrative concept embodied in the development of next-generation formulations helps to minimize bioavailability and safety issues with least or no adverse side effects and the provisional new dimensions presented in this direction may add value in the prevention and cure of complex chronic diseases.

Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.

Cancer is a deadly disease worldwide, with an anticipated 19.3 million new cases and 10.0 million deaths occurring in 2020 according to GLOBOCAN 2020. It is well established that carcinogenesis and cancer development are strongly linked to genetic changes and post-translational modifications (PTMs). An important PTM process, ubiquitination, regulates every aspect of cellular activity, and the crucial enzymes in the ubiquitination process are E3 ubiquitin ligases (E3s) that affect substrate specificity and must therefore be carefully regulated. A surfeit of studies suggests that, among the E3 ubiquitin ligases, neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4)/NEDD4-like E3 ligases show key functions in cellular processes by controlling subsequent protein degradation and substrate ubiquitination. In addition, it was demonstrated that NEDD4 mainly acts as an oncogene in various cancers, but also plays a tumor-suppressive role in some cancers. In this review, to comprehend the proper function of NEDD4 in cancer development, we summarize its function, both its tumor-suppressive and oncogenic role, in multiple types of malignancies. Moreover, we briefly explain the role of NEDD4 in carcinogenesis and progression, including cell survival, cell proliferation, autophagy, cell migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), chemoresistance, and multiple signaling pathways. In addition, we briefly explain the significance of NEDD4 as a possible target for cancer treatment. Therefore, we conclude that targeting NEDD4 as a therapeutic method for treating human tumors could be a practical possibility.