Current progress in the targeted therapy of breast cancer: Structure-activity correlation and docking studies (2015-2021).

Despite cancer research and therapy, breast cancer remains a complicated health crisis in women and represents a top biomedical research priority. Nowadays, breast cancer is an extremely heterogeneous disease and is known as the leading cause of death among women worldwide. The incidence and mortality rates of breast cancer have been increasing gradually for the past decades. Nowadays, common treatments for breast cancer are chemotherapy, endocrine therapy, immunotherapy, radiotherapy, and surgery. The most common targets in breast cancer treatment are human epidermal growth factor receptor 2 (HER2) and estrogen receptors. The literature suggests that several targets/pathways are also involved in the development of breast cancer, that is, poly(ADP-ribose) polymerase (PARP), bromodomain-containing protein 4 (BRD4), cyclin-dependent kinase 4/6 (CDK4/6), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), polo-like kinase 1 (PLK1), phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), histone deacetylase (HDAC), nuclear factor kappa B (NF-κB), PD-L1, and aromatase inhibitors. Meanwhile, the study of breast cancer is a hot topic in the current scenario of basic/clinical research. This review article provides information on different targets associated with breast cancer and summarizes the progress of current research on synthesized inhibitors as anti-breast cancer agents from 2015 to 2021. The review aims to provide structure-activity relationship and docking studies for designing novel compounds for breast cancer therapy.

Current Medicinal Insights on Synthetic Small Molecules and Natural Origin Products as PD-1/PD-L1 Inhibitors.

Cancer is one of the leading causes of death worldwide. Each year, millions of people are diagnosed with cancer; hence, researchers have always been curious and busy developing cancer treatments. Despite thousands of studies, cancer is still a major threat to human beings. One of the mechanisms through which cancer invades a human being is the immune escape mechanism, which has been the focus of studies in the past years. PD-1/PD-L1 pathway plays a major role in this immune escape. Therefore, research focusing on blocking this pathway has led to the discovery of molecules based on monoclonal antibodies that work quite well, but despite the successful application of monoclonal antibodies as inhibitors of the PD-1/PD-L1 pathway, there are some drawbacks, such as poor bioavailability and several immune-related adverse effects, which have led the researchers toward further investigation, thereby resulting in the discovery of different types of molecules, such as small molecule inhibitors, PROTAC-based molecules, and naturally derived peptide molecules that function as inhibitors of the PD-1/PD-L1 pathway. Here, in this review, we have summarized recent findings of these molecules and focused on their structural activity relationship. The development of these molecules has opened more prospects in cancer therapy.