Mesothelioma is a difficult cancer to treat for a multitude of reasons. A mesothelioma diagnosis is rare – only about 3,000 people per year in the United States are diagnosed – and this can make it difficult to study, given that there is generally a very small sample of patients that are able to be investigated. Additionally, the aggressive nature of the disease means that the cancer cells are able to quickly reproduce and are unable to respond to chemotherapy, rendering it ineffective in many (but not all) cases.
Pemetrexed and cisplatin are two FDA approved chemotherapy treatments that are found to be the most effective when treating those suffering from mesothelioma. However, these are the only two approved chemotherapy treatments despite decades of research and testing. The very nature of the cancer cells determine whether or not the cell will respond to treatment. Some cancer cells are naturally resistant to chemotherapy. Those cancer cells will survive, reproduce, and eventually saturate the body with chemo-resistant cancer cells. This is called intrinsic resistance. Other tumors may initially respond to the first few rounds of chemotherapy treatment, but eventually become resistant. The cells then begin to repair themselves and stop responding to treatment altogether. This is known as acquired resistance.
Cells, like all living organisms, are complex and are able to develop and adapt to do anything to prevent them from dying. Their cell membranes can sometimes alter so that chemotherapy is unable to enter. Furthermore, cells can also modify themselves so that chemotherapy treatment is expelled from the cell after it’s administered. Mesothelioma cells are also able to repair damage caused by cisplatin and even alter their DNA so cisplatin is unable to form a bond to the cancer cell.
How the treatment reaches the infected cells can also be compromised. When chemotherapy is administered, it moves to the infected cells through proteins. If these proteins become in effective, then they will not be able to do the job of carrying the chemotherapy to the cells and the unhealthy cells remain untouched.
Overcoming drug resistance is no small task, and scientists and researchers look to combination therapies to determine which treatment that is the most effective. This is why combination therapies are often used in mesothelioma patients. Combination treatments such as surgery and the chemotherapy, two different types of chemotherapy, or even the application of chemotherapy and immunotherapy, have shown promise over the years.
Additionally, the way that chemotherapy is administered can be beneficial. Certain methods such as hyperthermic intraperitoneal chemotherapy and hyperthermic intrathoracic chemotherapy deliver heated chemotherapy treatments after cancer -removing surgical procedures.
Source:
Caitriona Holohan, et. al. “Cancer drug resistance: an evolving paradigm,” Nature Reviews (September 24, 2013). [Link]
