image: Cancer cells project multiple extensions on their surface (visualized in red) to gain motility. PRL-3 (visualized in green) enhances this process by inducing activation of another potent cancer-causing gene, EGFR, thereby giving cancer cells the dangerous ability to rapidly spread to different organs. view more
Credit: A*STAR IMCB
A team of scientists led by Associate Professor Zeng Qi [1] from A*STAR's Institute of Molecular and Cell Biology (IMCB) have discovered a new biomarker which will help physicians predict how well cancer patients respond to cancer drugs. Having the means to identify patients who are most likely to benefit from currently available cancer drugs not only reduces substantially the healthcare cost for the patient, it could mean saving precious lives by getting the right drugs to the right patient at the onset of the treatment. This study published and featured on August cover of the Journal of Clinical Investigation will boost the development of personalised medicine in cancer care and therapy.
Metastasis is the rapid and uncontrollable spread of cancer cells from the primary tumour to other parts of the body. It is often the leading cause of death in cancer patients. Increasingly, there is evidence to show that in many cancers that have metastasised, a protein called PRL-3 is often found to be present at unusually high levels. Since it was first identified in 1998 by Associate Professor Zeng, several other research groups have found evidence to support the strong link between elevated levels of PRL-3 protein and the metastasis of aggressive cancers in the lung, liver, colon and breast. This cancer-promoting action of PRL-3 makes it an ideal target for cancer diagnostics and treatment.
In this study, the IMCB team discovered a curious synergy between PRL-3 and EGFR [2] , another well-known cancer-linked protein frequently associated with breast and lung cancers in humans. They found that cancer cells with higher levels of PRL-3 not only hyperactivate EGFR, but also develop an 'addiction' for it to survive. Consequently, by suppressing EGFR activity with EGFR inhibitor drugs, the scientists observed that cancer cells with higher levels of PRL-3 were more rapidly destroyed. To validate these findings in humans, the team collaborated with Associate Professor Wee Joo Chng [3] from the National University Health System to run an analysis on pre-existing clinical data of colorectal cancer patients. The results confirmed that patients who respond better to EGFR inhibitor drugs were those suffering from cancers with abnormally high levels of PRL-3.
Associate Professor Zeng said, "This unexpected synergy has revealed a vulnerable spot of aggressive cancers and brought new hope of treating PRL-3 driven cancers successfully. The addiction phenomenon we observed in cancer cells is akin to depriving alcohol from an alcoholic, thereby inducing the severe 'withdrawal effects'. In the same way, by selecting cancer patients with elevated levels of PRL-3 and greater 'addiction' of EGFR for anti-EGFR treatment, we can deliver more effective and targeted cancer therapy with the existing EGFR inhibitor cancer drugs."
Professor Sir David Lane, Chief Scientist of A*STAR said, "This is an excellent example of how years of basic research lay the foundation for advancement in translational and clinical applications. I am pleased that the team is exploring the potentials of developing this new predictive biomarker into a rapid diagnostic kit for identifying patients who will respond favourably to current anti-EGFR treatment. I believe that this study will open new avenues for personalised medicine in cancer therapy."
Footnote:
[1] For more information about Associate Professor Zeng Qi's lab http://www.imcb.a-star.edu.sg/php/qz.php
[2] Epidermal growth factor receptor (EGFR) is a cell surface protein that binds epidermal growth factor binds, causing cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so that these cancer cells may divide excessively in the presence of epidermal growth factor.
[3] http://www.ncis.com.sg/patient-and-visitors/find-a-doctor/associate-professor-chng-wee-joo.html
Notes for editor:
The research findings described in this media release can be found in the August issue of Journal of Clinical Investigation under the title, " Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells" by Abdul Qader Omer Al-aidaroos1, Hiu Fung Yuen1, Ke Guo1, Shu Dong Zhang2,Tae-Hoon Chung3, Wee Joo Chng3,4 and Qi Zeng1,5,*
1 Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore.
2 Center for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, United Kingdom.
3 Haematological Malignancy Genomics Lab, Cancer Science Institute of Singapore, National University of Singapore, Singapore.
4 Department of Haematology-Oncology, National University Cancer Institute, Singapore National University Health System, Singapore.
5 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
*Corresponding Author, Email: mcbzengq@imcb.a-star.edu.sg
Full text of the article can be accessed from http://www.jci.org/articles/view/66824
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About Institute of Molecular and Cell Biology (IMCB)
The Institute of Molecular and Cell Biology (IMCB) is a member of Singapore's Agency for Science, Technology and Research (A*STAR) and is funded through A*STAR's Biomedical Research Council (BMRC). It is a world-class research institute that focuses its activities on six major fields: Cell Biology, Developmental Biology, Genomics, Structural Biology, Infectious Diseases, Cancer Biology and Translational Research, with core strengths in cell cycling, cell signalling, cell death, cell motility and protein trafficking. Its achievements include leading an international consortium that successfully sequenced the entire pufferfish (fugu) genome. The IMCB was awarded the Nikkei Prize 2000 for Technological Innovation in recognition of its growth into a leading international research centre and its collaboration with industry and research institutes worldwide. Established in 1987, the Institute currently has 26 independent research groups, eight core facilities and 300 researchers.
For more information about IMCB, please visit http://www.imcb.a-star.edu.sg
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy. In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.
A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs, house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories.
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Journal
Journal of Clinical Investigation