Monisha Banerjee

MicroRNAs and HPV oncogenes crosstalk, their biomarker potential and therapeutic utility in cervical cancer

Cervical cancer remains a significant global health challenge, particularly in low-income regions, where incidence and fatality rates exceed WHO eradication limits. The miRNAs are emerging as crucial molecular markers in disease diagnostics and therapeutics. Their expression is influenced by Human Papillomavirus (HPV) infection leading to genomic instability and cervical carcinogenesis. The miRNA-based biomarkers exhibit potential for noninvasive identification in serum, urine, cervical mucus, exosomes, and tissue samples, and they also contribute to chemosensitization and resistance mechanisms. However, their clinical translation is hindered by multiple challenges. This review explores the mechanistic roles of miRNAs in HPV-mediated cervical cancer progression, their implications in diagnosis and therapy, and the barriers limiting their clinical application. Additionally, it outlines strategies to overcome translational hurdles, including combinatorial delivery, structural modifications, nanovehicles based delivery, viral vector systems, paving the way for miRNA-based interventions in cervical cancer management.

Potential of nano-phytochemicals in cervical cancer therapy

Cervical cancer is common among women with a recurrence rate of 35% despite surgery, radiation, and chemotherapy. Patients receiving chemotherapy or radiotherapy routinely experience several side effects including toxicity, non-targeted damage of tissues, hair loss, neurotoxicity, multidrug resistance (MDR), nausea, anemia and neutropenia. Phytochemicals can interfere with almost every stage of carcinogenesis to prevent cancer development. Many natural compounds are known to activate/deactivate multiple redox-sensitive transcription factors that modulate tumor signaling pathways. Polyphenols have been found to be promising agents against cervical cancer. However, applications of phytochemicals as a therapeutic drug are limited due to low oral bioavailability, poor aqueous solubility and requirement of high doses. Nano-sized phytochemicals (NPCs) are promising anti-cancer agents as they are required in minute quantities which lowers overall treatment costs. Several phytochemicals, including quercetin, lycopene, leutin, curcumin, green tea polyphenols and others have been packaged as nanoparticles and proven to be useful in nano-chemoprevention and nano-chemotherapy. Nanoparticles have high biocompatibility, biodegradability and stability in biological environment. Nano-scale drug delivery systems are excellent source for enhanced drug specificity, improved absorption rates, reduced drug degradation and systemic toxicity. The present review discusses current knowledge in the involvement of phytochemical nanoparticles in cervical cancer therapy over conventional chemotherapy.

Cytokine gene variants and treatment outcome of cisplatin-based concomitant chemoradiotherapy in cervical cancer

Genetic and epigenetic alterations in DNA repair genes and treatment outcome of chemoradiotherapy in cervical cancer

Cervical cancer (CaCx) is the deadliest malignancy among women which is caused by human papillomavirus (HPV) and anthro-demographical/clinicopathological factors. HPV oncoproteins E6 and E7 target p53 and RB (retinoblastoma) protein degradation, Ataxia telangiectasia mutated (ATM), ATM-RAD3-related (ATR) inactivation and subsequent impairment of non-homologous end joining (NHEJ), homologous recombination, and base excision repair pathways. There is also an accumulation of genetic and epigenetic alterations in Tumor Growth Suppressors (TGS), oncogenes, and DNA repair genes leading to increased genome instability and CaCx development. These alterations might be responsible for differential clinical response to Cisplatin-based chemoradiotherapy (CRT) in patients. This review explores HPV-mediated DNA damage as a risk factor in CaCx development, the mechanistic role of genetic and epigenetic alterations in DNA repair genes and their association with CRT and outcome, It also explores new possibilities for the development of genetic and epigenetic-based biomarkers for diagnostic, prognostic, and molecular therapeutic interventions.

Enhanced therapeutic efficacy of Piperlongumine for cancer treatment using nano-liposomes mediated delivery

Piperlongumine (PL) is a well-known bioactive alkaloid that has been reported as a potent anticancer molecule but has failed to provide potential activity in translational and clinical applications due to some drawbacks like low bioavailability, hydrophobicity, and rapid degradation. However, nano-formulation is a good choice to increase the bioavailability and enhance cellular uptake of PL. In this study, PL loaded nano-liposomes (NPL) were formulated using the thin-film hydration method and analyzed by Response Surface Methodology (RSM) in order to treat cervical cancer. The NPL were thoroughly characterized using particle size, PDI, zeta potential, drug loading capacity, encapsulation efficiency, SEM, AFM and FTIR. Different assays viz. MTT, AO/PI, DAPI, MMP, cell migration, DCFDA and apoptotic assay using Annexin V-FITC/PI were performed for anticancer potential of NPL in human cervical carcinoma cells (SiHa and HeLa). NPL showed enhanced cytotoxicity, diminished cell proliferation, reduced cell viability, enhanced nuclear condensation, reduction in mitochondrial membrane potential, inhibited cell migration, increased ROS level and promoted more apoptosis in both human cervical cancer cell lines. These findings demonstrated that NPL may be a potential therapeutic option for cervical cancer.