Comprehensive somatic mutational analysis in glioblastoma: Implications for precision medicine approaches.

Glioblastoma multiforme (GBM), a malignant neoplasm originating from glial cells, remains challenging to treat despite the current standard treatment approach that involves maximal safe surgical resection, radiotherapy, and adjuvant temozolomide chemotherapy. This underscores the critical need to identify new molecular targets for improved therapeutic interventions. The current study aimed to explore the somatic mutations and potential therapeutic targets in GBM using somatic mutational information from four distinct GBM datasets including CGGA, TCGA, CPTAC and MAYO-PDX. The analysis included the evaluation of whole exome sequencing (WES) of GBM datasets, tumor mutation burden assessment, survival analysis, drug sensitivity prediction, and examination of domain-specific amino acid changes. The results identified the top ten commonly altered genes in the aforementioned GBM datasets and patients with mutations in OBSCN and AHNAK2 alone or in combination had a more favorable overall survival (OS). Also, the study identified potential drug sensitivity patterns in GBM patients with mutations in OBSCN and AHNAK2, and evaluated the impact of amino acid changes in specific protein domains on the survival of GBM patients. These findings provide important insights into the genetic alterations and somatic interactions in GBM, which could have implications for the development of new therapeutic strategies for this aggressive malignancy.

Current trends and future prospects of drug repositioning in gastrointestinal oncology.

Gastrointestinal (GI) cancers comprise a significant number of cancer cases worldwide and contribute to a high percentage of cancer-related deaths. To improve survival rates of GI cancer patients, it is important to find and implement more effective therapeutic strategies with better prognoses and fewer side effects. The development of new drugs can be a lengthy and expensive process, often involving clinical trials that may fail in the early stages. One strategy to address these challenges is drug repurposing (DR). Drug repurposing is a developmental strategy that involves using existing drugs approved for other diseases and leveraging their safety and pharmacological data to explore their potential use in treating different diseases. In this paper, we outline the existing therapeutic strategies and challenges associated with GI cancers and explore DR as a promising alternative approach. We have presented an extensive review of different DR methodologies, research efforts and examples of repurposed drugs within various GI cancer types, such as colorectal, pancreatic and liver cancers. Our aim is to provide a comprehensive overview of employing the DR approach in GI cancers to inform future research endeavors and clinical trials in this field.

Fanconi Anemia Pathway in Colorectal Cancer: A Novel Opportunity for Diagnosis, Prognosis and Therapy.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and has the second highest mortality rate globally. Thanks to the advent of next-generation sequencing technologies, several novel candidate genes have been proposed for CRC susceptibility. Germline biallelic mutations in one or more of the 22 currently recognized Fanconi anemia (FA) genes have been associated with Fanconi anemia disease, while germline monoallelic mutations, somatic mutations, or the promoter hypermethylation of some FANC genes increases the risk of cancer development, including CRC. The FA pathway is a substantial part of the DNA damage response system that participates in the repair of DNA inter-strand crosslinks through homologous recombination (HR) and protects genome stability via replication fork stabilization, respectively. Recent studies revealed associations between FA gene/protein tumor expression levels (i.e., FANC genes) and CRC progression and drug resistance. Moreover, the FA pathway represents a potential target in the CRC treatment. In fact, FANC gene characteristics may contribute to chemosensitize tumor cells to DNA crosslinking agents such as oxaliplatin and cisplatin besides exploiting the synthetic lethal approach for selective targeting of tumor cells. Hence, this review summarizes the current knowledge on the function of the FA pathway in DNA repair and genomic integrity with a focus on the FANC genes as potential predisposition factors to CRC. We then introduce recent literature that highlights the importance of FANC genes in CRC as promising prognostic and predictive biomarkers for disease management and treatment. Finally, we represent a brief overview of the current knowledge around the FANC genes as synthetic lethal therapeutic targets for precision cancer medicine.

Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature.

Brain metastasis (BM) is the most common event in patients with lung cancer. Despite multimodal treatments and advances in systemic therapies, development of BM remains one of the main factors associated with poor prognosis and mortality in patients with lung cancer. Therefore, better understanding of mechanisms involved in lung cancer brain metastasis (LCBM) is of great importance to suppress cancer cells and to improve the overall survival of patients. Several cancer-related genes such as EGFR and KRAS have been proposed as potential predictors of LCBM. In addition, there is ample evidence supporting crucial roles of non-coding RNAs (ncRNAs) in mediating LCBM. In this review, we provide comprehensive information on risk assessment, predictive, and prognostic panels for early detection of BM in patients with lung cancer. Moreover, we present an overview of LCBM molecular mechanisms, cancer driver genes, and ncRNAs which may predict the risk of BM in lung cancer patients. Recent clinical studies have focused on determining mechanisms involved in LCBM and their association with diagnosis, prognosis, and treatment outcomes. These studies have shown that alterations in EGFR, KRAS, BRAF, and ALK, as the most frequent coding gene alterations, and dysregulation of ncRNAs such as miR-423, miR-330-3p, miR-145, piR-651, and MALAT1 can be considered as potential biomarkers of LCBM.

Development of curcumin-loaded gemini surfactant nanoparticles: Synthesis, characterization and evaluation of anticancer activity against human breast cancer cell lines.

BACKGROUND: Curcumin, the polyphenolic constituent of turmeric, has been recognized as an effective anticancer agent in the treatment of breast cancer. However, the poor bioavailability of curcumin triggers finding of new approaches for elevating its therapeutic efficiency. PURPOSE: We aimed to use gemini surfactant nanocarriers for curcumin in order to overcome its limitations. STUDY DESIGN: We investigated the in vitro characterization of gemini surfactant-curcumin (Gemini-Cur) and examined its antiproliferative & apoptotic activities on breast cancer cell lines. METHODS: Gemini-Cur polymersomes were synthesized through nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission and scanning electron microscopies, HPLC and X-ray diffraction (XRD). The anticancer effect of Gemini-Cur nanoparticles was studied on three different breast cancer cell lines including MCF-7, SkBr-3 and MDA-MB-231 through uptake kinetics, viability & cytotoxicity recordings and apoptotic assays. Furthermore, qRT-PCR was performed to evaluate the expression of apoptotic genes including p16INK4a, p14ARF, Bax and Bcl-2. RESULTS: According to physicochemical analysis, the average particle size, zeta potential value and drug entrapment efficiency for Gemini-Cur compound were recorded as 161 ±â€¯6.2 nm, +5.32 mV and 89.13% ±â€¯0.93, respectively. XRD analysis also confirmed the incorporation of curcumin in gemini surfactant micelles. Regarding the enhanced cellular uptake of sphere shaped Gemini-Cur, our data showed that this nano compound suppresses cancer cell proliferation via induction of apoptosis. Moreover, qRT-PCR analysis revealed that Gemini-Cur could effectively upregulate the expression of p16INK4a, p14ARF and Bax, while significantly decreasing the Bcl-2 expression in these breast cancer cells. CONCLUSION: Our data demonstrates the great potential of gemini surfactants for efficient delivery of curcumin and subsequently, the improvement of its anticancer effect. Therefore, it is sagacious to support the idea that Gemini-Cur nano compound might have the potential to be considered as an anticancer agent.