Cancer

Diagnosed each year in one in every 250 men and one in every 300 women(WHO).

Clonal in origin

Six hallmarks

1. Immortality eg. HeLa cells

2. Produces GO signal, ie proto-oncogenic protiens

3. Override STOP signals (TSGs inactivation)

4. Resist cell death

5. Angiogenesis

6. Metastasis

Treatments available

Radiotherapy Chemotherapy Hormone therapy Cytokines Monoclonal antibodies Gene therapy

Gives rise to all type of cells present in an organism. E.g., embryonic stem cells derived from blastocyst

INDUCED PLURIPOTENCY

iPSCs were first produced in 2006 from mouse epidermal fibroblast cells

In 2007, iPSCs were derived from human cells by Shinya Yamanaka's team at Kyoto University, Japan

Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent

Mouse iPSCs

Human iPSCs

Takahashi and Yamanaka, Cell, Aug 25, 2006

iPSc Generation

Potentials of iPS cellsPotentials of iPS cells

Ability to differentiate into many cell types

Easily accessible

Individual-specific i.e. personalized or non-immunogenic

Vastly renewable

Useful for studying mechanisms of disease

Useful for drug, toxicity testing

Application of the hiPSCs

Application in cancer

Disease modeling

Immuno therapy

Immunotherapy

• Immune system fails to effectively fight the tumor.

Tumor tolerence

Weak response

Defending property

• autologous immune enhancement

Dendritic cell vaccines(iPSDCs)

T-cell therapies

NK-cell therapies

Contd…..

• Antitumor monoclonal antibodies

block growth signals

stops angiogenesis

Drug/radiation delivery

• Cancer vaccines

Disease modeling

• Best model to study cancer pathogenesis is primary patient sample.

• iPSCs can be generated from cancer cells.

• Can use for

Pancreatic Ductal Adenocarcinoma(PDAC)

Chronic myeloid Leukemia(CML)

Juvenile Mylomonocytic Leukemia(JMML)

Obstacles in therapeutic application of iPSCs in humans

• Use of harmful oncogenes as part of the reprogramming factors.

• Use of viral vectors for gene delivery that carry the risk of insertional mutagenesis.

• Low efficiency and slow kinetics of reprogramming.

• Lack of robust and reliable differentiation protocols for human iPS cells

Conclusion

• Discovery of iPSC is a remarkable boost to research and therapy

• Offered a new field for cancer research and future possible applications in the clinical practice.

• use of hiPSCs may contribute to the development of future personalized cell therapies and open new possibilities

References1. Seung-Ick Oh, Chang Kyu Lee, Kyung Jin Cho,Kyung-Ok

Lee, Ssang-Goo Cho, and Sunghoi Hong; Technological Progress in Generation of Induced Pluripotent Stem Cells for Clinical Applications, The Scientific World Journal ,10 (2012),1-10

2. MartinezMatthias Stadtfeld and Konrad Hochedlinger; Induced pluripotency: history, mechanisms and applications, Genes & Development, 24 (2010), 2239–2263

3. Timothy J Nelson, Almudena , Fernandez, SatsukiYamada,Yasuhiro Ikeda, Carmen Perez-Terzic, Andre Terzic; Induced pluripotent stem cells: advances to applications, Stem Cells and Cloning: Advances and Applications,3 (2010), 29-37

4. Eamon Geoghegan and Lucy Byrnes; Mouse induced pluripotent stem cells, The International Journal of Developmental Biology, 52, (2008), 1015-1022

5. Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita,Tomoko Ichisaka, Kiichiro Tomoda and Shinya Yamanaka; Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,Cell, 131, (2007), 1–12