The Origin of Cancer Secrets Revealed

文:张元吉教授

Cancer is common and the leading cause of death in Singapore and many parts of the world. The first thing for us to learn to conquer cancer is to know its origin. Cancer is considered as a group of diseases resulted from accumulation of multiple genetic and epigenetic abnormalities (mutations). These transforming mutations change the look and biological behaviour of cancer cells, so the cancer cells can have unlimited growth potential, invade and metastasize to other organs of the host, evade immune surveillance, obtain immortality and other malignant activities.

There are 3 major sources of mutation:hereditary (inherited), environment (exposure to carcinogens) and spontaneous (random mutation during normal DNA replication) or by interaction of all 3 elements. According to the analysis of Dr. Vogelstein and Tomasetti from Johns Hopkins University, the proportion of heritable cancers is only 5~10%, environmental factors account for 25~30%, and the rest 65% of cancer are due to random mutation. Different strategies are indicated for different scenarios. For example, bilateral mastectomy would be recommended for female patients with inheritable BRCA1 or BRCA2 mutation by removing the source of end organ ie. breast, thus avoiding cancers. Another example is to stop smoking which is most efficacious in reducing smoking induced cancers, such as lung concern in heavy smokers. However, for patients with non-smoking related lung cancer, stop smoking would not impact much the incidence of this kind of lung cancer but still benefit in reducing other type of cancers and other complications from smoking. On the other hand, screening mammogram and colonoscopy are shown to reduce mortality of cervical cancer, breast cancer and colorectal cancer, they are helpful for early diagnosis.

There are multiple mutations in a single cancer patient. Scientists need to identify dominant driver mutations which are responsible for malignant behaviour. These driver mutations then become the targets and/or bio markers for developing successful therapy, this is called the targeted therapy. The cancer cells can vary in their driver mutation even in the same tumour mass from one patient. The prevalence of driver mutations also have geographic and ethnic differences suggesting different etiology and biology even in the same kind of cancer. This is called heterogeneity of cancer indicating every cancer has its own characteristics and requires individualized treatment. There are currently many successful targeted treatments for cancer patients and more yet to come. Truly personalised medical treatment for cancer patients is within reach soon. This is a great improvement to check and look forward to.

We also know that the development of overt or gross tumour mass takes a long time, varying from few years to 10~20 years or longer. Genet changes occur in every steps of the transformation from normal to hyperplasia (means too many normal looking cells) to dysplasia (means abnormal cells and tissue structure) to carcinoma to invasion and metastases. Cancer has a very long latent period before it becomes clinically detectable. Therefore, cancer does not develop overnight. In practice, we classify cancer diseases into 4 stages for treatment recommendation and prognostication. Radical surgery is usually the treatment of choice for early stage I and II diseases which are confined in one location of the body. Surgery and/or radiation or radiation/chemotherapy are recommended for stage III disease with regional lymph node involvement. Chemotherapy, targeted therapy, immunotherapy or radiation/surgery are used for stage IV with metastatic disease to control the disease. Indeed, there are many treatment options tailored to fit every individual patient to cure or prolong the survival. One should not overlook this fact.

In conclusion, we begin to understand how cancer comes from and develop strategies to deal with. Some cancers are preventable, some cancers can be diagnosed early. Effective treatments are available for most cancer patients. Continuous improvement of treatment results is expected as we continue to reveal the secrets of cancer.