Dr. Weeks’ Comment: Because Ms. Jolie never asked informed oncologists (who were keeping up with the research), she was never told that cancer TUMOR cells are not the problem and ought not be targeted (chemo -radiation, surgery) because the lethal cancer cell is actually the cancer STEM cell – which is not killed by conventional care. (Dr. Wicha says Chemo and radiation make your cancer worse.”) She would have saved her breasts and her ovaries and her uterus. Now the world is learning what Angelina was never told: the cancer STEM cells, which are made “more numerous and more virulent” by chemotherapy and radiation, are the important target.
So if you happen to know Angelina, please tell her to focus on her lethal cancer STEM cells. That is lifesaving advice and I’d enjoy seeing more of her movies in the years ahead. (hint: she needs to eat whole, ground organic non-GMO seeds...)
“…Is there a mastermind that is responsible for all such ghastly events in cancer? In recent years, a potential culprit called cancer stem cells have been discovered, which are thought to be responsible for metastasis, relapses and drug resistance...”
A complex disease
A LONG-TIME friend Grace came into my office in tears one day. She was upset as her father and elder brother had died of cancer. And her younger brother had been diagnosed with colon cancer but chemotherapy was not working. She wondered if she would be diagnosed with cancer too. She asked why people were still dying of cancer every day despite all the cancer research.
Grace’s grief is not uncommon. We all know someone, including our immediate family, who has died of cancer.
There are at least two issues in Grace’s grief, namely a familiar trait of cancer risk, and why chemotherapy treatment often fails in cancer treatment. Though not identified, Grace’s family most likely carries one or more “faulty” genes, each of which has a 50% chance of passing on to the next generation.
Cancer and cancer stem cells
Cancer is a complex disease. Besides hereditary genetic factors, cancer is horrendous in four other aspects, namely that: (i) cancer cells divide rapidly and uncontrollably; (ii) cancer cells can spread or metastasise to other body sites; metastasis is the major cause of cancer death; (iii) cancers can relapse or re-grow after surgical removal or other treatments; (iv) cancers often develop resistance to therapeutic drugs, therefore depriving cancer patients the use of a powerful armoury to combat the disease.
Is there a mastermind that is responsible for all such ghastly events in cancer? In recent years, a potential culprit called cancer stem cells have been discovered, which are thought to be responsible for metastasis, relapses and drug resistance.
Cancer stem cells (CSC) are present in a tumour mass in a very minute population. These cells are called cancer stem cells because they share the features of normal stem cells, which are the good guys, in being able to differentiate to give rise to other cell types. CSC may, therefore, generate multiple tumours through the self-renewal and differentiation properties of stem cells, leading to relapses and also giving the cancer cells mobility to spread to distant sites.
How does cancer develop resistance to chemotherapeutic drugs? Such an event is again linked to cancer stem cells. In the cell membrane of all normal cells, there are pumping stations, such as the ABC transporters, which are responsible for moving small molecules across the membrane. In cancer stem cells, such pumping stations are hyperactive in actively pumping out, and therefore removing therapeutic drugs from inside of the cancer cells. So while other surrounding cancer cells are being killed by the drug, cancer stem cells selectively survive the drug onslaught, and slowly become enriched in the tumour mass.
The discovery of cancer stem cells has shifted our thinking in battling cancer. Instead of just aiming to shrink the size of a tumour mass, it may now be imperative to think in terms of a search-and-destroy mission, targeting at cancer stem cells.
The CSC concept has provided new directions of designing novel therapeutic approaches to treat cancers. For example, all cells have a unique set of specific markers on the cell surface. Cancer stem cell-specific markers that distinguish them from other cancer or normal cells are being identified. Drugs may be developed to home in on such CSC-specific markers to selectively destroy CSC.
An example of such a drug, salinomycin, a veterinary drug, has indeed been identified by a team of Massachusetts Institute of Technology/ Harvard University scientists to be highly potent in killing CSCs. A common Indian spice, curcumin, also appears to be a CSC killer. As a further precaution, such drugs may be encapsulated in nanoparticles for controlled drug release in clinical protocols.
Stem cell-based therapy
The stem cell concept has also led to the development of stem cell-based cancer therapy. Prof Hans-Peter Kiem and his team at the Fred Hutchinson Cancer Research Centre, in Seattle, the United States, have developed “stem cell shield” to protect normal tissues, particularly the blood-generating bone marrow cells, from side effects of the anti-cancer drugs. Dr Khalid Shah of Massachusetts General Hospital and Harvard Medical School has genetically engineered stem cells into mini drug armouries to produce and secret toxin that specifically kills only brain tumours sparing normal cells.
In another angle of thinking, can we rein in cancer cells by reprogramming them into something else more controllable and less vicious? Prof Shinya Yamanaka from Kyoto University, Japan, was awarded the Nobel Prize in Physiology and Medicine in 2012 for developing a protocol for “reprogramming” cells to induce pluripotent stem cells, or iPSC. These reprogrammed cells have all the characteristics of stem cells in being able to convert into any cell types for regenerative purposes.
At the Faculty of Medicine and Health Sciences and the Centre of Stem Cell Research, Universiti Tunku Abdul Rahman (UTAR), we are the first in Malaysia to report on successful reprogramming of a number of cancer types into induced pluripotent cancer (iPC) cells, which are temporarily frozen in their expression of cancer features. Such iPCs are valuable in drug screening, in finding ways to reboot the damaged DNA repair mechanisms, and to be used as cancer study model in general.
Reprogramming can also be personalised because the reprogrammed cancer cells of a patient still carry the full set of delirious mutations. Such personalised reprogrammed cancer cells may then be used for rapid and accurate identification of the most effective drug for that particular cancer patient.
Cancer is so complex that it may never be totally conquered. The discovery of cancer stem cells and the use of stem cell-based cancer therapeutic approaches may only be a small but significant step towards the better tackling of cancer. Lots of work needs to be done, but we should remain hopeful that laboratory findings will one day be translated into clinical applications.
After that outburst in my office, I visited Grace when she calmed down. I told her that researchers may not have conquered cancer but they are still working hard to improve survival rates and the quality of life for cancer patients.
“Please do remember that the many vaccines we and our children use as preventive measures against diseases, the many drugs that allow us to control diabetes or blood pressure or cholesterol, the many diagnostic and therapeutic instruments and protocols that are being used daily worldwide to save lives are also the products of the efforts of hardworking researchers. Medical research is never a waste of taxpayers’ money. Medical research saves lives.”
Senior Professor Dr Choo Kong Bung is from the Faculty of Medicine and Health Sciences and Centre for Stem Cell Research chairman, Universiti Tunku Abdul Rahman.
This is a series of articles on Science, Technology, Engineering and Mathematics from Universiti Tunku Abdul Rahman.