RESUMEN
Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.
RESUMEN
Approximately 90% of malignancies have been shown to have human telomerase activity, establishing it as a viable therapeutic target. The crystal structure of telomerase was determined recently. However, the tertiary structure of the non-conserved flexible linker region remains unresolved. This study aims to predict the full-length tertiary structure of the human telomerase reverse transcriptase (hTERT). Two strategies were employed to determine the full-length structure of hTERT (1132 amino acids); iterative threading and a conjoined model generated from machine learning and energy functions. After energy minimization, Ramachandran Plot analysis, and simulation; the conjoined model was considered of better quality and stability. The linker region of the conjoined depicted two helices from approximately 275-284 and 201-211 amino acids respectively in contrast to the iterative threading model which has a single helix. Moreover, the region was observed to undergo major structural changes throughout the simulation. These changes signify its flexibility which might be due to the region having a significant number of glycine and proline and could enhance the clamping movement.Communicated by Ramaswamy H. Sarma.
RESUMEN
Cancer is one of the major causes of mortality worldwide, therefore it is considered a major health concern. Breast cancer is the most frequent type of cancer which affects women on a global scale. Various current treatment strategies have been implicated for breast cancer therapy that includes surgical removal, radiation therapy, hormonal therapy, chemotherapy, and targeted biological therapy. However, constant effort is being made to introduce novel therapies with minimal toxicity. Gene therapy is one of the promising tools, to rectify defective genes and cure various cancers. In recent years, a novel genome engineering technology, namely the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9) has emerged as a gene-editing tool and transformed genome-editing techniques in a wide range of biological domains including human cancer research and gene therapy. This could be attributed to its versatile characteristics such as high specificity, precision, time-saving and cost-effective methodologies with minimal risk. In the present review, we highlight the role of CRISPR/Cas9 as a targeted therapy to tackle drug resistance, improve immunotherapy for breast cancer.