For over a century, scientists have painstakingly worked to find the ultimate causes of cancers, hoping this could point to a cure for the disease. Many disparate agents are known to be associated with cancers: cigarette smoke, soot, asbestos, radiation, alcohol, chemicals, and others. But exactly how they lead to cancer is not entirely clear.
The cellular origins of cancer had been a mystery until the turn of the 21st century, when the inner molecular workings of a normal cell came into sharper focus. Genetic change (gene mutations) is now the most pervasive answer we hear from researchers. Errors in DNA duplication during cell division and DNA damaged by toxic substances, such as tobacco, alcohol, and UV light exposure, all have supporting medical evidence confirming them as causes of cancer. The mutated gene can be hereditary, passed on in the family from generation to generation if it occurs in a germ cell. Sometimes, a viral infection can trigger cancer cell growth.
New mutations occur in our bodies every single day throughout our lifetimes. More than a million mutations happen in our DNA daily; the sites where most of these mutations occur don't have significant consequences. Most mutated genes do not contribute to cancer development unless they happen in proto-oncogenes and/or tumour suppressor genes. These genes encode proteins that sit at the hub of cell signalling pathways, which are highly regulated in normal cells. Proto-oncogenes are normal cellular genes that, when mutated, their encoded proteins become permanently activated, causing uncontrolled, rapid cell proliferation. On the other hand, mutations in tumour suppressor genes that put a brake on cell proliferation led to loss of the encoded proteins' function and the absence of growth-inhibitory signals, which contributed to unregulated, rapid cell growth.
Fortunately, one mutation isn't usually sufficient to turn a cell cancerous. Most cancer developments are likely a multi-step process in which normal cells gradually progress to malignancy. That cancer is not more common considering the number of mutations occurring is because of various cellular protective mechanisms. There are repair systems for damaged DNA, heavily damaged cells can self-destruct, and a cancer cell also needs to evade an immune system that is constantly keeping an eye out and getting rid of abnormal cells before they accumulate the right set of mutations to turn into cancerous cells.
Cancer is one of the top three leading causes of death in Thailand. According to the WHO Global Cancer Observatory 2020 database, one in six people of both sexes in Thailand will develop cancer before the age of 75. Liver and bile duct, lung, and colorectal cancers, on the one hand, and breast, colorectal, and cervical cancers, on the other hand, are the three most common cancers in males and females, respectively. This differs from Caucasians, where skin melanoma, a rare cancer in Asians, is very common. Statistics indicate that race/ethnicity exerts an influence on the incidence of certain types of cancer more than others. White females are slightly more prone to breast cancer than black females, but breast cancers in black women tend to be more aggressive. Two-thirds of cancer occurs in people over 60, simply because they have had more time to accumulate the necessary mutations for cancer emergence. On the contrary, certain cancers are more prevalent in children or young people, such as leukaemia, lymphoma, and germ cell tumours, which are sometimes curable.
The secular trends of cancer incidence in Asian countries over the past decade are increasing, particularly in females and younger populations aged below 40. However, the cancer mortality rate over the same period is declining, reflecting better treatment outcomes and early detection. The burden of cancer can be mitigated by avoidance of known risk factors and early detection through screening where possible and available, especially for high-incidence cancers such as mammography, pap smears, gastroscopy, colonoscopy, and low-dose CT for lung cancer in high-risk subjects, which is strongly recommended.
There are many cancer treatment modalities. The treatment regimen will depend on the type of cancer and how advanced it is. Some people with early-stage cancer will need only one treatment modality, usually a local form such as surgery or radiation therapy. But most cancer patients will require a combination of surgeries, chemotherapy, hormonal, and radiation therapy. Nowadays, novel treatments have moved on from traditional chemotherapy with systemic side effects to targeted therapy and immunotherapy based on new cancer biology knowledge on the abnormal molecular signalling pathways of cancer cells. Targeted therapy inhibits the signalling pathway that drives that type of cancer cell proliferation. Both treatments are less toxic and more effective; they can be used in combination with chemotherapy in certain situations.
Recently, the development of new genomic sequencing technology, Next-Generation Sequencing (NGS), with much faster turnaround times, has been increasingly utilised in cancer genomics research. NGS has been incorporated as an innovative cancer treatment strategy to identify true driver gene mutations in cancer in an individual patient. This technology provides the molecular basis for selecting pharmacologic agents in a personalised treatment approach and predicts treatment efficacy over standard therapy. Based on this genomic information, patients may receive a different targeted therapy or regimen even though they have the same cancer type at the same stage because cancer genomes are disparate, composed of a mishmash of different cell groups, each with their own unique mutations.
It is worth noting that we have come a long way since the early days of the first effective chemotherapeutic agent nearly a century ago. Unlike other diseases, cancer, particularly at an advanced stage, is rarely curable. Thanks to novel treatment modalities, some patients with incurable cancer can live for many years with a good quality of life. As mentioned, cancer is a complex disease with multiple risk factors and causes. Researchers have tried to sort out the relative contributions of environmental and inherited causes.
But mostly, we still do not know the complete sequence of events required for the development of any given instance of human cancer, and this is why many cancers are still not preventable or curable. Dr. Cristian Tomasetti and Dr. Bert Vogelstein of Johns Hopkins University School of Medicine, put forth the "bad luck" hypothesis, suggesting that only one-third of cancers are attributable to environmental or inherited factors. The majority is due to "bad luck," that is, random mutations occurring during DNA replication in normal cells. If patients subscribe to this theory, they might feel less guilty and disheartened about past unhealthy lifestyles. Because the past cannot be altered and taken back, equanimity is what cancer patients should strive for in the present, hoping for a scientific breakthrough to effect a cure.
Author: Dr. Sudpreeda Chainitikun, Medical Oncologist, MedPark Hospital
Series Editor: Katalya Bruton, Healthcare Content Editor and Director, Dataconsult Ltd. Dataconsult's Thailand Regional Forum at Sasin provides seminars and documentation to update on business trends in Thailand and the Mekong Region. Contact: info@dataconsult.co.th, Tel: 662-233-5606/7
