| Albert Einstein, the Great Man of Science wrote: | | | | (cell death) and motility. At the early stage of |
| "It is theory that decides what we can observe." | | | | carcinogenesis (cancer process) TGF-beta is a |
| If our mind is set (biased by the theory that we | | | | potent inhibitor of cell proliferation but at later |
| have learnt in school) then "that is all" that we can | | | | stages of carcinogenesis the levels of TGF-beta |
| see - we can't see anything beyond what we | | | | increase with tumour progression. It is not known |
| have learnt or been taught! It needs an | | | | how TGF-beta switches it role from being a |
| open-minded person to "see" what others do not | | | | tumour suppressor to being a promoter during |
| want to see or fail to see. | | | | the course of cancer progression. |
| For twenty-six years, I devoted two lectures in | | | | Many disease processes are associated with loss |
| my physiology class to teaching university | | | | of normal TGF-beta function, such as cancer, |
| students understand the Scientific Method. The | | | | atherosclerosis, autoimmune and inflammatory |
| first step for any scientific discovery is | | | | diseases. Excessive TGF-beta production have |
| OBSERVATION of a phenomenon. If you cannot | | | | been implicated in the formation of scar tissues or |
| or don't want to "see" how can you ever | | | | fibrosis (in lung and liver), development of |
| discover anything new? | | | | pulmonary edema (fluid in lung), |
| After more than a decade working with cancer | | | | immunosuppression and successful parasite |
| patients there is one phenomenon that I had | | | | infection. |
| observed: " breast cancer patients tend to suffer | | | | TGF-beta has been said to cause chronic |
| metastasis (spread) to their lungs, bones, etc. | | | | pulmonary (lung) fibrosis in rats and mice exposed |
| pretty soon after undergoing medical treatments." | | | | to chemo-drugs, bleomycin or cyclophosphamide, |
| Of course, some doctors may scream at such a | | | | and in the development of hepatic (liver) fibrosis in |
| suggestion! I wonder if this "hunch" is an illusion? | | | | rats exposed to radiation. |
| The answer came on 7 April 2007, in the form of | | | | TGF-beta has been shown to promote breast |
| a small, insignificant column in The Star. It had this | | | | cancer metastasis by acting directly on the |
| heading: "Study: Treatment may fuel cancer's | | | | tumour cells. TGF-beta is also shown to enhance |
| spread." The study reported in the Journal of | | | | parathyroid-hormone-related protein (PTHrP) and |
| Clinical Investigation by Dr. Carlos Arteaga and | | | | subsequently resulted in bone destruction in breast |
| colleagues at Vanderbilt University, USA, showed | | | | cancer patients. Advanced breast cancer patients |
| that treating cancer with surgery, chemotherapy | | | | have been shown to have increased plasma |
| or radiation may sometimes cause tumours to | | | | TGF-beta levels after chemotherapy and |
| spread. In their work they used doxorubicin (a | | | | TGF-beta is positively associated with disease |
| common chemo-drug used for breast cancer) or | | | | progression. |
| radiation and found that these treatments raised | | | | Dr. Carlos Arteaga and colleagues showed that |
| levels of TGF-beta, which in turn helped breast | | | | when mice infected with human breast cancer |
| cancer tumours to spread to the lung. The | | | | were treated with radiation or doxorubicin, they |
| researchers wrote: "The repopulation and | | | | had higher levels of TGF-beta in their blood. They |
| progression of tumours after anti-cancer therapy | | | | also had more tiny tumour cells in their blood and |
| (such as radiotherapy, chemotherapy and | | | | these cells spread to the lungs. When the mice |
| surgery) is a well-recognised phenomenon." | | | | were treated with antibody that suppresses |
| How many of us (doctors and patients alike) | | | | TGF-beta, the spread stopped. The spreading |
| know this? If doctors know, do they tell their | | | | process did not occur at all in mice bred to lack |
| patients? If patients know, what is their | | | | TFG-beta. |
| response? | | | | Comments: What are the implications of the |
| After reading this report, I spent a whole morning | | | | above? When you are asked to do chemo or |
| surfing the web to learn more about this | | | | radiation, ask first what is the main objective of |
| phenomenon. This is what I learnt. The key to our | | | | such a treatment - to cure? to prevent cancer |
| understanding is a biological protein called | | | | from spreading? or what. This study showed that |
| Transforming Growth Factor beta (TGF-beta). | | | | treatments like chemotherapy or radiation cause |
| TGF-beta exists in at least five (iso)forms, known | | | | the spread of cancer. This report is a direct |
| as TGF beta 1, beta 2, beta 3, beta 4 and beta 5. | | | | opposite of what you are often told about the |
| The roles of TGF-beta in cancer are very | | | | purpose of chemotherapy or radiotherapy - i.e., to |
| complex and often confusing indeed. TGF-beta | | | | kill the cancer cells or stop them from spreading! |
| controls cell proliferation, differentiation, apoptosis | | | | |