: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

Enzyme aromatase uses several androgen substrates for the biosynthesis of estrogen, i.e. conversion of androstenedione to estrone and testosterone to biologically potent estradiol. Aromatase inhibitors (AIs) such as anastrozole, letrozole and exemestane have been established in standard endocrine therapy of breast cancer, by interfering with estrogen signaling cascade. Steroid sulphatase (STS) regulates the level of active oestrogens and androgens in human target organs and steroidogenic tissues, which have a key role in hormone dependent breast cancers (HDBC). Sulfatase is still under the exploration stage and is yet to emerge as a potential therapeutic target in breast cancer. The discovery of estrone 3-O-sulfamate (EMATE), a highly potent irreversible STS inhibitor, accelerated the development of potent steroidal and nonsteroidal STS inhibitors. Attempts are also being made for the development of dual inhibitors of AI and STS, as an alternative approach to overcome the acquired resistance. This review includes the molecular structures and biochemistry of aromatase and sulphatase enzymes. The advances in the development of inhibitors of the two enzymes have also been outlined.