Question

Outline the molecular changes required for initiation and progression of colorectal cancer. How could these molecular changes be exploited to assist with diagnosis and treatment?

Selective differentiation of iPSCs can be used to generate a broad range of cell types. Outline how iPSCs reprogramming is currently being applied for cancer research. Discuss how this technology can improve our ability to model cancer behaviour for more efficient drug discovery.

Outline the epigenetic changes starting with a differentiated cell, to the partially reprogrammed cells and finally the iPSC.

Answer 1

Ansy ý Colarectal cancer + A malignant tumoli auking from Inner wall of the large intestine (colon) risk factor for Cancer of Colon and rectum (colorectal Cancer include colon polyps, long standing, ulcerative colitis, and genetic family history. - (CRC) is a heterogenous disease, developing through a multipathway sequence of event guided by clonal sélection, pathway included in the development of cRc may be broadly Catagorized into a genomic Instab- -ility, (MSI) and (CPG) 6) gemmic mutation including suppression of tumor suppressor gene and activation of tumell onlogene) C microRNA and a) Epigentic change. A Cancer become more advanced , invasion and metastases are fucilitated through epithelial mesenchymal tran- sition with additional genetic alternation: (CRC) second leading cause of cancer related death in men and women combined / 1) with a third of CRC patient dying from this - disease 2) It is theorized , initiated and progress in a unique manner that is not necessarily identical amongst all tumors.

3 As a result, the focus of CRC research is shifting from a clinical perspective towards developing an understanding of molecular basis of this mali- gnancy including inclividual susceptibility development progression response and resist- -ance to antitumar treatment and metastatic spread. Cancer develops through multiple and sequential genetic alternations - Through clonal selection the cancer cell "chooses the genetic alternation the most conducere to growth through proliferation of cells that posses the desired qulities with apoptosis of those that do not - A more thorough understanding of these molecular pathway may contribute to improved strategies for prevention scree- ing diagnosis and therapy. And > Ilsce • Induced pluripotent stem cells in Cancer research. It is a present a Mange of new opportunities for the Study of human cancer.

forsty, IPSC, a unique status as Cancer models are intimately linked to their properties as pluri- potent cells, their unlimited sell. Mehewal offer the opportunity to capture the entire intact genome of a single cells and amplify it into an unlimited number of copies Second their broad development potential offer the opportunity to examine the effect of specific cancer genotype or a specific cancer genotype or a specific driver mutation, a mutation thought to drive oncogenesis in different cell type and developmental stage providing a unique system through which to address questions such as whether a specific tissue restricted exigenctic enviroment is requred for an oncogenic potential Coooo ipses to Person matcheda oo Omarmal 7 Normal Tissue studies had clone Prevolution Clonal y subclone I progression Cooperation and order to a gyako Tumor derived Coop Rebrogermming matched B ayout Genotype to phenotype .

Cancer ! - Differentiation Lake stage Ecorly stage Cancer Bioengineering Reprogramming ocell based therapy Tissue reconstrution Cancer modeling • pathways organ replacement Biomarkers • Toxicology esome Normal Tissue • Dang screening Concer ipses lines ating B 7 Predisposed tissue 835999 cell type of interest ) Epigentic change - A Cancer develops when acell acquires specific growth advantages through the stepwise accumulation of heritable Change in gene function 0 0 Epigenetic alternatin which by defination comprise mitotically and melotically heritable changes in gene expression that are not caused by changes in primary DNA sequence, are increasingly long Mecognized for their role in carcinogenesis, Ans

Accordingly the and histone target for new clinical view DNA methylation - modification are very allorachve development and implementation therapeutic apperches : many clinical epigentic therehy administratian the treatment trials are ongoing and has recently been (USADA) for we in. (MDS) and (CTCL).