Pancreatic Cancer

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Pancreatic cancer therapy using engineered mesenchymal stem cells

description

mesenchymal stem cells engineering

Transcript of Pancreatic Cancer

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Pancreatic cancer therapy using engineered mesenchymal stem

cells

 

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Pancreas

• Two functions -  Exocrine and endocrine• Exocrine: The acinar cells generate digestive enzymes. Ductal cells secrete bicarbonate and mucous. Tumour originates from Ductal tissue(95%).

• Endocrine: Islets- β-cells - insulin, α-cells - glucagon, δ-cells – somatostatin, PP cells - pancreatic polypeptide, ε cells - ghrelin. Tumour originates from islet cells (2-4%).

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Pancreatic Cancer

• According to 2012 cancer statistics, pancreatic  cancer is ranked 10th in terms of new cancer cases and 4th in cancer deaths.

• Pancreatic cancer presents in up to 50% at a locally advanced stage dramatically reducing the chance of curative resection

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Pathways - AKT

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WNT pathway

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Therapies

• Current: – Chemotherapy– Palliative surgery – to relieve pain 

• New therapeutic strategies can be categorized as:– RNA interference/ antisense oligonucleotides that inhibits the activated oncogenes.

– restore function of the tumor suppressor genes

• Gene therapy using engineered MSCs with anticancer genes in order to target pancreatic cancer cell lines.

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Mesenchymal stem cells

• Group of adult stem cells, sourced from bone marrow.

• Capable of differentiating into tissue of muscle, vascular system, and connective tissue.

• Use of MSCs in therapeutics : easy and fast acquisition ex vivo and ease of transfection.

• Due to tumour migration and incorporation capacity, engineered MSCs together with anticancer genes can be used as a delivery vector to treat pancreatic cancer cells.

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Anticancer activity of MSCs

 MSCs engineered with anticancer genes are capable of specifically attacking tumour cells through multiple mechanisms :

• tumour-directed migration and incorporation• anticancer agent delivery

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Tumour-directed migration

• Advancing tumours continuously produce cytokines, chemokines, and other inflammatory mediators. 

• Such signals are capable of attracting respondent cell types such as MSCs.

• IL-8, neurotrophin-3, TGF-, IL-1, TNF-a, platelet-derived growth factor, and EGF have also been shown to enhance MSCs tumour tropism capabilities.

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Anticancer agent delivery

• Wnt pathway-induced apoptosis– Inhibitor of Wnt - Sostdc1(Sclerostin domain-containing protein 1)

• Supression of AKT pathway– Inhibitor of PI3K(tumour suppressor PTEN)

• Suicide genes- TK gene and GCV gene

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Expected personalized treatment of pancreatic cancer with engineered mesenchymal stem cells

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