RESUMEN

Cancer cells undergo metabolic reprogramming to survive in hypoxic conditions and meet the elevated energy demands of the cancer microenvironment. This metabolic alteration is orchestrated by hypoxia-inducible factor 1 (HIF-1), regulating various processes within cancer cells. The intricate metabolic modifications induced by hypoxia underscore the significance of HIF-1-induced metabolic reprogramming in promoting each aspect of cancer progression. The complex interactions between HIF-1 signalling and cellular metabolic processes in response to hypoxia are examined in this study, focusing on the metabolism of carbohydrates, nucleotides, lipids, and amino acids. Comprehending the various regulatory mechanisms controlled by HIF-1 in cellular metabolism sheds light on the intricate biology of cancer growth and offers useful insights for developing targeted treatments.

Asunto(s)

Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Animales , Factor 1 Inducible por Hipoxia/metabolismo , Microambiente Tumoral , Transducción de Señal , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Reprogramación Celular , Reprogramación Metabólica

RESUMEN

Nuclear factor κB (NF-κB) is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions. NF-κB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells. NF-κB is the only signaling molecule that governs both pro- and anti-apoptotic, and pro- and anti-inflammatory responses. This is due to the canonical and non-canonical components of the NF-κB signaling pathway. Together, these pathways orchestrate cancer-related inflammation, hyperplasia, neoplasia, and metastasis. Non-canonical NF-κB pathways are particularly involved in the chemoresistance of cancer cells. In view of its pivotal role in cancer progression, NF-κB represents a potentially significant therapeutic target for modifying tumor cell behavior. Several phytochemicals are known to modulate NF-κB pathways through the stabilization of its inhibitor, IκB, by inhibiting phosphorylation and ubiquitination thereof. Several natural pharmacophores are known to inhibit the nuclear translocation of NF-κB and associated pro-inflammatory responses and cell survival pathways. In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-κB component, we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-κB signaling pathways for controlling the fate of tumor cells for cancer-directed interventions.

RESUMEN

Cancer Stem Cells (CSCs) are a notoriously quiescent subpopulation of cells within heterogeneous tumors exhibiting self-renewal, differentiation and drug-resistant capabilities leading to tumor relapse. Heterogeneous cell populations in tumor microenvironment develop an elaborate network of signalling and factors supporting the CSC population within a niche. Identification of specific biomarkers for CSCs facilitates their isolation. CSCs demonstrate abilities that bypass immune surveillance, exhibit resistance to therapy, and induce cancer recurrence while promoting altered metabolism of the bulk tumor, thereby encouraging metastasis. The fight against cancer is prone to relapse without discussing the issue of CSCs, making it imperative for encapsulation of current studies. In this review, we provide extensive knowledge of recent therapeutics developed that target CSCs via multiple signalling cascades, altered metabolism and the tumor microenvironment. Thorough understanding of the functioning of CSCs, their interaction with different cells in the tumor microenvironment as well as current gaps in knowledge are addressed. We present possible strategies to disrupt the cellular and molecular interplay within the tumor microenvironment and make it less conducive for CSCs, which may aid in their eradication with subsequently better treatment outcomes. In conclusion, we discuss a brief yet functional idea of emerging concepts in CSC biology to develop efficient therapeutics acting on cancer recurrence and metastasis.

Asunto(s)

Neoplasias , Células Madre Neoplásicas , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Recurrencia , Microambiente Tumoral , Cordón Umbilical/patología

RESUMEN

Nuclear factor κB(NF-κB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-κB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells.NF-κB is the only signaling molecule that governs both pro-and anti-apoptotic,and pro-and anti-inflammatory responses.This is due to the canonical and non-canonical components of the NF-κB signaling pathway.Together,these pathways orchestrate cancer-related inflammation,hyperplasia,neoplasia,and metastasis.Non-canonical NF-κB pathways are particularly involved in the chemoresistance of cancer cells.In view of its pivotal role in cancer progression,NF-κB represents a potentially significant therapeutic target for modifying tumor cell behavior.Several phy-tochemicals are known to modulate NF-κB pathways through the stabilization of its inhibitor,IKB,by inhibiting phosphorylation and ubiquitination thereof.Several natural pharmacophores are known to inhibit the nuclear translocation of NF-κB and associated pro-inflammatory responses and cell survival pathways.In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-κB component,we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-κB signaling pathways for controlling the fate of tumor cells for cancer-directed interventions.