Cancer is caused by a complex interaction of factors that interrupt the normal growth and division of cells. At the center of this process is the intricate relationship between DNA damage and the cellular mechanisms responsible for maintaining genomic stability. When DNA damage is not repaired, it can cause genetic mutations that contribute to the initiation and progression of cancer. On the other hand, the DNA damage response system, which involves the phosphorylation of the histone variant H2AX (γH2AX), is crucial in preserving genomic integrity by signaling and facilitating the repair of DNA double-strand breaks. This review provides an explanation of the molecular dynamics of H2AX in the context of DNA damage response. It emphasizes the crucial role of H2AX in recruiting and localizing repair machinery at sites of chromatin damage. The review explains how H2AX phosphorylation, facilitated by the master kinases ATM and ATR, acts as a signal for DNA damage, triggering downstream pathways that govern cell cycle checkpoints, apoptosis, and the cellular fate decision between repair and cell death. The phosphorylation of H2AX is a critical regulatory point, ensuring cell survival by promoting repair or steering cells towards apoptosis in cases of catastrophic genomic damage. Moreover, we explore the therapeutic potential of targeting H2AX in cancer treatment, leveraging its dual function as a biomarker of DNA integrity and a therapeutic target. By delineating the pathways that lead to H2AX phosphorylation and its roles in apoptosis and cell cycle control, we highlight the significance of H2AX as both a prognostic tool and a focal point for therapeutic intervention, offering insights into its utility in enhancing the efficacy of cancer treatments.

Angiogenesis is defined as the physiological process by which new blood vessels develop from pre-existing vessels; either by sprouting or intussusception. Inhibition of angiogenesis is one of the most encouraging strategies to manage the growth and metastasis of cancers. The functional and proliferative status of blood vessels is regulated by the balance between various key molecules that either stimulate or inhibit angiogenesis. During quiescence, the “angiogenic switch” is “off”. However, during tumour development pro-angiogenic factors such as vascular endothelial growth factor (VEGF), basic and acidic fibroblast growth factor, tumour necrosis factor-α and interleukin-1 are pathologically enhanced. Persistent growth of tumour directed capillary networks creates a favourable microenvironment, promoting cancer growth, progression and metastasis. VEGF, particularly VEGF-A, is a key angiogenic factor. Targeting VEGF, its receptors and the downstream signaling cascade, is a viable strategy to prevent tumour growth and metastasis. The present review discusses the role of VEGF in tumour angiogenesis and the current understanding of anti-VEGF therapies as well as refractoriness of anti-angiogenesis cancer therapy.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.

Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc. NRTKs exhibit considerable variability in their structural make up, having a shared kinase domain and commonly possessing many other domains such as SH2, SH3 which are protein-protein interacting domains. Recent studies show that NRTKs are mutated in several hematological malignancies, including lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due to point mutations which are intragenic changes or by fusion of genes leading to chromosome translocation. Mutations that lead to constitutive kinase activity result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore, specific kinase inhibitors have been sought after to target mutated kinases. A number of compounds have since been discovered, which have shown to inhibit the activity of NRTKs, which are remarkably well tolerated. This review covers the role of various NRTKs in the development of hematological cancers, including their deregulation, genetic alterations, aberrant activation and associated mutations. In addition, it also looks at the recent advances in the development of novel natural compounds that can target NRTKs and perhaps in combination with other forms of therapy can show great promise for the treatment of hematological malignancies.

Since the introduction of the cancer stem cell (CSC) paradigm, significant advances have been made in understanding the functional and biological plasticity of these elusive components in malignancies. Endowed with self-renewing abilities and multilineage differentiation potential, CSCs have emerged as cellular drivers of virtually all facets of tumor biology, including metastasis, tumor recurrence/relapse, and drug resistance. The functional and biological characteristics of CSCs, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation are regulated by an array of extracellular factors, signaling pathways, and pluripotent transcriptional factors. Besides the well-characterized regulatory role of transcription factors OCT4, SOX2, NANOG, KLF4, and MYC in CSCs, evidence for the central role of Forkhead box transcription factor FOXM1 in the establishment, maintenance, and functions of CSCs is accumulating. Conventionally identified as a master regulator of the cell cycle, a comprehensive understanding of this molecule has revealed its multifarious oncogenic potential and uncovered its role in angiogenesis, invasion, migration, self-renewal, and drug resistance. This review compiles the large body of literature that has accumulated in recent years that provides evidence for the mechanisms by which FOXM1 expression promotes stemness in glioblastoma, breast, colon, ovarian, lung, hepatic, and pancreatic carcinomas. We have also compiled the data showing the association of stem cell mediators with FOXM1 using TCGA mRNA expression data. Further, the prognostic importance of FOXM1 and other stem cell markers is presented. The delineation of FOXM1-mediated regulation of CSCs can aid in the development of molecularly targeted pharmacological approaches directed at the selective eradication of CSCs in several human malignancies.