The document discusses the transformation of normal cells into cancerous cells, focusing on therapeutic strategies targeting the transforming growth factor-β (TGF-β) signaling pathway for cancer prevention and treatment. It highlights the dual roles of TGF-β in tumor suppression and progression, as well as approaches for inhibiting TGF-β signaling in cancer therapy. Additionally, it covers chemoprevention methods and challenges associated with TGF-β's impact on cancer metastasis.

1. SCT60103
Genes & Tissue Culture Technology
Group 1:
By: BRAVIEN KOFFMAN, JOANNE THERESA,
HARIS URSILAN, VAISNEVEE, VIKNESHWARAN
Topic: A normal cell can be transformed into a cancerous
cell. Discuss the therapeutic strategies that are employed
to target the cellular transformation process for cancer
prevention and treatment.

2. Introduction
➔ Transformation cancer cause
genetic instability.
➔ Effects of the transformation.
◆ Growth rate,
◆ Mode of growth,
◆ Life span
◆ Product formation
◆ Tumorigenicity
➔ Causes of transformation.
◆ Virus
◆ Gene transfection
◆ Chemical carcinogens
◆ Ionizing radiation
Figure 1: Stages of colon cancer
(Helpconstipation.net, 2014).

3. “AN EXCELLENT SERVANT, BUT A BAD MASTER”
What is TGF-β?
It is a protein that performs many cellular functions such as control of cell
growth, cell proliferation, cell differentiation and apoptosis (Khalil 1999).
How does TGF beta link to cancer ?
● TGF-β signaling pathways exert tumor suppressor effects in normal cells
and early carcinomas by inducing:
1. Apoptosis
2. Preventing cell immortalization
3. Inhibiting the cell cycle.
● As tumors develop and progresses, these protective and cytostatic effects
of TGF-β are often lost.
● While expression of TGF itself is often increased in human tumors,
expression of the genes encoding various components of the TGF
signaling cascade (receptor type I and type II, Smad2, Smad3, and Smad4)
are often mutated or deleted in human cancer.
● When this happens, The TGF-β signaling then switches to promote cancer
progression, invasion, and tumor metastasis.
(Lebrun, 2012).
1. Targeting the transforming Growth Factor-β signaling in
cancer therapy.
Treatment
Figure 2: Pathway of TGF-β
signalling pathway

4. ● TGF beta protein-receptor interactions
promotes growth and metastasis of cancer
cells.
● Hence, to inhibit TGF beta signalling
pathway, 4 methods has been identified:
1. Using monoclonal TGF-β-neutralizing
antibodies to inhibit ligand-receptor
interaction
2. Using large molecule ligand traps
3. Reducing translational efficiency of TGF-β
ligands using antisense technology
4. Antagonizing TGF-β receptor I/II kinase
function by small molecule inhibitors to
inhibit receptor-mediated signaling.Figure 3: TGF-Beta Protein- receptor
interaction

5. Chemoprevention
➔ Cancer chemoprevention is the
use of substances to stop cancer
from developing. These substances
may be natural or made in the
laboratory.
➔ Is typically used for people who
have a higher risk of developing
cancer.
➔ Can be divided into;
◆ Immunotherapy
◆ Epigenetics
◆ Dietary
(Cancer. Net, 2017).
➔ Study of heritable changes
in gene expression that
does not change the
underlying sequence of
DNA.
➔ Epigenetics drugs are
developed to revert cancer
cell back to normal.

6. ➔ Most studied epigenetics
◆ Methylation of DNA - Methyl
group is added DNA strand. If
methyl group attached to genes
that are regulating cell growth
and cell division it causes
disruption in the normal
function.
◆ Histone Protein modifications -
Protein that DNA wraps around.
It regulates how tight or how
loose the DNA wraps around the
protein. If it swirl around too
tight then the gene cannot
undergo the normal translation
and if it's too loose then it might
activate genes that should
remain silent.
➔ Drug Development
◆ Azacitidine and decitabine-
inhibits DNA
methyltransferase. Used in
myelodysplastic syndrome.
◆
SAHA or vorinostat- Histone
deacetylases (HDACs), affects
the ability of histone to be
wrapped by DNA. Used in
treating T- Cell lymphoma,
immune cell cancer in the
skin.
(Grisham 2017)

7. Challenges
➔ The signalling pathway of TGF-B also
has a major role in the progression of
tumor (Connolly et al. 2012).
➔ TGF-B can cause Epithelial to
Mesenchymal Transition (EMT) ,
whereby epithelial cells become
mesenchymal stem cells,which are
able to initiate cancer metastasis (Xu
et al. 2009).
Figure 4 : Dual roles for TGF-B signalling during tumorigenesis
1. TGF-β

8. Conclusion
As cancer rates continues to increase, the demand for cure and
prevention has increased over-time as well. However, with the enhancement of
modern technology, the cure and prevention for cancer has gotten more
realistic and achievable. Treatments such as radiation therapy, surgery,
chemotherapy, hormonal therapy and immunotherapy has definitely made a
huge breach in terms of cure and prevention in the medical history.

9. Connolly, E., Freimuth, J. and Akhurst, R 2012, ‘Complexities of TGF-β Targeted Cancer Therapy’, International Journal of
Biological Sciences, 8(7), pp.964-97, Viewed on 11 September 2017, <
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399319/>
Grisham, J 2017, What Is Epigenetics?, Memorial Sloan Kettering Cancer Center, Viewed on 14 September 2017, <
https://www.mskcc.org/blog/what-epigenetics>
Grisham, J 2017, The future of Cancer research; five reasons for optimism, Memorial Sloan Kettering Cancer Center, Viewed
on 11 Sept3ember 2017, < https://www.mskcc.org/blog/future-five-reasons-optimism>
Kroschinsky, F., Stölzel, F., von Bonin, S., Beutel, G., Kochanek, M., Kiehl, M. and Schellongowski, P 2017, New drugs, new
toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Critical Care, 21(1),
Viewed on 10 September 2017, < https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399319/>
Lebrun, J 2012, The Dual Role of TGF-β in Human Cancer: From Tumor Suppression to Cancer Metastasis, ISRN Molecular
Biology, Viewed on 13 September 2017 < https://www.hindawi.com/journals/isrn/2012/381428/>
Xu, J., Lamouille, S. and Derynck, R. 2009, TGF-β-induced epithelial to mesenchymal transition. Cell Research, 19(2), Viewed
on 13 September 2017 < https://www.ncbi.nlm.nih.gov/pubmed/19153598>
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