A comprehensive review on anticancer mechanism of bazedoxifene

Abstract

Cancer is counted as a second leading cause of death among nontransmissible diseases. Identification of novel anticancer drugs is therefore necessary for the effective treatment of cancer. Conventional drug discovery is time consuming and expensive process. Unlike conventional drug discovery, drug repositioning offers a novel strategy for urgent drug discovery since it is a cost-effective and faster process. Bazedoxifene (BZA) is a synthetic selective estrogen receptor modulator, approved by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. BZA is now being studied for its anticancer activity in various cancers including breast cancer, liver cancer, pancreatic cancer, colon cancer, head and neck cancer, medulloblastoma, brain cancer, and gastrointestinal cancer. Studies have reported that BZA is effective in reducing cancer progression through multiple mechanisms. BZA could effectively inhibit STAT3, PI3K/AKT, and MAPK signaling pathways and induce apoptosis. In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib, and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets, and anticancer mechanism of BZA, which may help the further design and conduct of research and repositioning it for oncological clinic trials.

Targeting Breast Cancer: An Overlook on Current Strategies

“…Bazedoxifene (Duavive ® ) is a synthetic SERM, which received approval by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. It is now being studied as a repositioned drug for its anticancer activity in different types of cancers including BC [ 58 ]. Recently, the combination of BZA and palbociclib showed clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR + /HER2 − BC [ 59 ].…”

Selective estrogen receptor modulators in post-menopausal osteoporosis

“…Recent studies have shown that bazedoxifene has potent anticancer activity in several types of cancer [30,44] . These properties, which are now being studied both in vitro and in vivo, make bazedoxifene a promising anticancer drug.…”

Vitamin K: A novel cancer chemosensitizer

“…4 The reason behind increasing cases is complex and reflects aging, population growth, and inefficient treatment along with prevalence and distribution of main risk factors of cancer, most of which are associated with socioeconomic development. 2 Chemotherapy, radiation therapy, hormone therapy, immune therapy, targeted therapy, surgery, and laser therapy are currently being used in cancer treatment. 5,6 Despite these advancements, the promising option for cancer treatment is chemotherapy.…”

“…Its global burden is expected to be 28.4 million cases in 2040 4 . The reason behind increasing cases is complex and reflects aging, population growth, and inefficient treatment along with prevalence and distribution of main risk factors of cancer, most of which are associated with socioeconomic development 2 …”

“…Cancer represents the second leading cause of death and the most important barrier for increasing life expectancy globally in the twenty-first century. 1,2 It is a diverse and mechanistically complex disease with a plethora of underlying genetic causes characterized by uncontrolled cell division and proliferation because of accumulating a large series of genetic alterations which confer a significant cause of morbidity and mortality in many countries around the world. 3 According to Global Cancer Statistics, approximately 19.3 million new cancer cases and 10.0 million deaths by cancer were reported in 2020.…”