pathways which would require the use of multiple therapeutic approaches in order to prevent pro-metastatic events via emt induction in cancer cells by activated platelets. to improve the chances for the development of a cancer metastasis, a cancer cell must avoid detection and targeting by the immune system once it enters the bloodstream. activated platelets have the ability to bind glycoproteins and glycolipids (p-selectin ligands such as psgl-1) on the surface of cancer cells to form a physical barrier that protects the cancer cell from natural killer cell-mediated lysis in the bloodstream. furthermore, activated platelets promote the adhesion of cancer cells to activated endothelial cells lining blood vessels using adhesion molecules present on platelets. p-selectin ligands on the surface of cancer cells remain to be elucidated and may serve as potential biomarkers for disease progression in cancer. therapeutics targeting cancer emt many studies have proposed that induction of emt is the primary mechanism by which epithelial cancer cells acquire malignant phenotypes that promote metastasis. drug development targeting the activation of emt in cancer cells has thus become an aim of pharmaceutical companies. small molecule inhibitors small molecules that are able to inhibit tgf-β induced emt are under development. silmitasertib (cx-4945) is a small molecule inhibitor of protein kinase ck2, which has been supported to be linked with tgf-β induced emt, and is currently in clinical trials for cholangiocarcinoma (bile duct cancer), as well as in preclinical development for hematological and lymphoid malignancies. in january 2017, silmitasertib was granted orphan drug status by the u.s. food and drug administration for cholangiocarcinoma and is currently in phase ii study. silmitasertib is being developed by senhwa biosciences. another small molecule inhibitor galunisertib (ly2157299) is a potent tgf-β type i receptor kinase inhibitor that was demonstrated to reduce the size, the growth rate of tumors, and the tumor forming potential in triple negative breast cancer cell lines using mouse xenografts. galunisertib is currently being developed by lilly oncology and is in phase i/ii clinical trials for hepatocellular carcinoma, unresectable pancreatic cancer, and malignant glioma. small molecule inhibitors of emt are suggested to not act as a replacement for traditional chemotherapeutic agents but are likely to display the greatest efficacy in treating cancers when used in conjunction with them. antagomirs and microrna mimics have gained interest as a potential source of therapeutics to target emt induced metastasis in cancer as well as treating many other diseases. antagomirs were first developed to target mir-122, a microrna that was abundant and specific to the liver, and this discovery has led to the development of other antagomirs that can pair with specific micrornas present in the tumor microenvironment or in the cancer cells. a microrna mimic to mir-655 was found to suppress emt through the targeting of emt inducing transcription factor zeb1 and tgf-β receptor 2 in a pancreatic cancer cell line. overexpression of the mir-655 mimic in the panc1 cancer cell line upregulated the expression of e-cadherin and suppressed the migration and invasion of mesenchymal-like cancer cells. the use of microrna mimics to suppress emt has expanded to other cancer cell lines and holds potential for clinical drug development. however, microrna mimics and antagomirs suffer from a lack of stability in vivo and lack an accurate delivery system to target these molecules to the tumor cells or tissue for treatment. improvements to antagomir and microrna mimic stability through chemical modifications such as locked nucleic acid (lna) oligonucleotides or peptide nucleic acids (pna) can prevent the fast clearing of these small molecules by rnases. delivery of antagomirs and microrna mimics into cells by enclosing these molecules in liposome-nanoparticles has generated interest however liposome structures suffer from their own drawbacks that will need to be overcome for their effective use as a drug delivery mechanism. these drawbacks of liposome-nanoparticles include nonspecific uptake by cells and induction of immune responses. the role that micrornas play in cancer development and metastasis is under much scientific investigation and it is yet to be demonstrated whether microrna mimics or antagomirs may serve as standard clinical treatments to suppress emt or oncogenic micrornas in cancers. generation of endocrine progenitor cells from pancreatic islets similar to generation of cancer stem cells, emt was demonstrated to generate endocrine progenitor cells from human pancreatic islets. initially, the human islet-derived progenitor cells (hipcs) were proposed to be better precursors since β-cell progeny in these hipcs inherit epigenetic marks that define an active insulin promoter region. however, later, another set of experiments suggested that labelled β-cells de-differentiate to a mesenchymal-like phenotype in vitro, but fail to proliferate; thus initiating a debate in 2007. since these studies in human islets lacked lineage-tracing analysis, these findings from irreversibly tagged beta cells in mice were extrapolated to human islets. thus, using a dual lentiviral and genetic lineage tracing system to label β-cells, it was convincingly demonstrated that adult human islet β-cells undergo emt and proliferate in vitro. also, these findings were confirmed in human fetal pancreatic insulin-producing cells, and the mesenchymal cells derived from pancreatic islets can undergo the reverse of emt – met – to generate islet-like cell aggregates. thus, the concept of generating progenitors from insulin-producing cells by emt or generation of cancer stem cells during emt in cancer may have potential for replacement therapy in diabetes, and call for drugs targeting inhibition of emt in cancer. partial emt or a hybrid e/m phenotype not all cells undergo a complete emt, i.e. losing their cell-cell adhesion and gaining solitary migration characteristics. instead, most cells undergo partial emt, a state in which they retain some epithelial traits such as cell-cell adhesion or apico-basal polarity, and gain migratory traits, thus cells in this hybrid epithelial/mesenchymal (e/m) phenotype are endowed with special properties such as collective cell migration. two mathematical models have been proposed, attempting to explain the emergence of this hybrid e/m phenotype, and its highly likely that different cell lines adopt different hybrid state(s), as shown by experiments in mcf10a, hmle and h1975 cell lines. although a hybrid e/m state has been referred to as 'metastable' or transient, recent experiments in h1975 cells suggest that this state can be stably maintained by cells.