درمان های مولکولی

Colorectal cancer ranks as the third most prevalent cancer and stands as the second foremost cause of mortality globally. The median overall survival for individuals with previously untreated advanced colorectal cancer has improved to a range of 25 to 30 months, attributed to the integration of molecularly targeted therapies alongside chemotherapy. The main approach for managing unresectable metastatic colorectal cancer involves systemic therapy, which encompasses cytotoxic chemotherapy, biologic therapies like antibodies targeting cellular growth factors, immunotherapy, and various combinations of these modalities. Recent clinical trials conducted over the last five years have shown that customizing treatment based on the molecular and pathological characteristics of the tumor can enhance overall survival rates. The utilization of genomic profiling to identify somatic variants is crucial, as it helps pinpoint potentially effective treatment options.

This investigation examined the significance of targeted therapy in the treatment of patients with metastatic colorectal cancer, alongside an evaluation of emerging therapeutic strategies, through a comprehensive review of diverse literature pertaining to various approaches in the management of colorectal cancer.

Treatment approaches for localized colorectal cancer predominantly involve surgical intervention and chemotherapy. In contrast, strategies for managing metastatic colorectal cancer are advancing, particularly through the identification of biomarkers that facilitate targeted therapies. These include inhibitors of the epidermal growth factor receptor (EGFR), serine/threonine-protein kinase B-Raf (BRAF), enhanced human epidermal growth factor receptor 2 (HER2), immune checkpoint inhibitors, and neurotrophic receptor tyrosine kinase (NTRK) inhibitors. Current predictive biomarkers for patients with metastatic colorectal cancer encompass mutations in RAS (rat sarcoma virus), BRAF mutations, microsatellite instability (MSI), mismatch repair deficiency (dMMR), HER2 amplifications, and NTRK fusions. The primary challenge lies in the effective integration of these advancements into routine clinical practice.

This review examines the contemporary predictive biomarkers relevant to patients with metastatic colorectal cancer and their corresponding targeted therapies. It highlights novel factors influencing anti-EGFR treatments, including the location of the primary tumor and the evaluation of immunosuppressants for microsatellite instability (MSI). Additionally, it addresses recent advancements in the treatment of BRAFV600E mutated cancers, as well as the roles of anti-HER2 therapies and NTRK inhibitors.

Peroxisome proliferator-activated receptors (PPARs), belonging to the superfamily of nuclear receptors, serve as transcription factors upon ligand binding, either with endogenous or synthetic ligands, forming heterodimers with Retinoid X Receptors (RXRs). They initiate gene transcription to harmonize lipid and carbohydrate metabolism with cell proliferation and differentiation. Fatty acids and their derivatives are natural ligands. To date, three subtypes of PPARs have been identified: PPARα, PPARγ, and PPARβ/δ, each having drug agonists and antagonists developed. Furthermore, universal agonists have been designed to target combinations of these subgroups to mitigate drug side effects. PPARs control cellular energy homeostasis and are also expressed in immune cells, where they play a vital role in their differentiation and fate. Given the significant impact of PPAR activity on both innate and adaptive immune cell function and their involvement in immune-related diseases, e.g. antiphospholipid syndrome, hepatitis, myocarditis, neurodegenerative diseases, psoriasis, asthma, inflammatory bowel disease, renal inflammation and atherosclerosis, it is conceivable to treat some of these diseases by modulating these transcription factors. Furthermore, due to the significance role of PPARs in regulating tissue metabolism, several instances of them have been investigated.

Breast cancer is always one of the most important difficulties in women''s health that causes serious physical، mental and economical harms for the patient and her family. Nowadays، molecular therapies have been considered by the researchers. Used drugs act through different molecular mechanisms and prevents from breast cancer developing; a lot of proteins play a role in these mechanisms including melatonin has a specific role. For this reason، recognizing melatonin functions and executive mechanisms، related genes and orientation with melatonin news and also its benefits in breast cancer will help us to design new and efficient molecular methods in treatment and management of breast cancer. This study was performed with the aim to review recognized mechanisms by melatonin in breast cancer treatment till now. To open access the articles، we searched from valid internal and external databases. For research formula، at first، we determine main key words، then equivalent terms were identified، and using appropriate operators، the formula was developed. The results were screened and the relevant articles were selected. Finally، 55 articles about breast cancer molecular biology and Melatonin function mechanism were selected and based on them، the review was done. The wide function domain of Melatonin in breast cancer includes induction of apoptosis، telomerase and inhibition of epidermal growth factor bridle in breast cancer، cell cycle inhibition، stimulation of immune system to destroy cancer cells، repair of damaged DNA، the regulation of daily and seasonal rhythm and also angiogenesis inhibition. The role of melatonin as an oncostatics and oncocytotoxic factor leads to believe melatonin application as a supplement factor in breast cancer treatment. The safety of Melatonin along with its benefits introduces it as a suitable candidate to improve treatment methods for breast cancer patients.