Metastasis Affected by Drug Resistance

Cancer is a term used to refer to the uncontrolled growth of abnormal cells in the body. This can happen in any part of the body, and as a result, there are over 200 types of cancer.1 Similarly, the signs and symptoms of cancer depend on the specific type and grade of cancer a person has, though there are certain generalized signs and symptoms that can be found in most cancer patients, such as weight loss, pain, fatigue, skin changes, fever, lumps, changes in bowel or bladder functions, and others.2

All around the world, cancer today has a significant impact on society. In 2018 alone, an estimated 1,735,350 new cases of various types of cancer were diagnosed in the United States, and over 600,500 people died from the disease.3 Caner has today become one of the leading causes of death all over the world, and over 8.2 million cancer-related deaths were recorded worldwide in 2012. This number seems to be growing each year, and by the end of 2030, the number of new cancer cases is expected to cross 23.6 million.4, 5

Metastasis and a Reduced Survival Rate for Cancer Patients

While the mortality rate of cancer varies depending on the type and grade of cancer, there is one more major reason behind why people die from cancer. This is known as metastasis. Metastasis is the process that enables certain cancer cells inside the body to break off from their tumor of origin and travel in the body to take root in a different tissue somewhere else.6

To date, the exact process in which tumors spread inside the body and kill off their host tissue remains a mystery. However, the process of metastasis takes place when the genetically unstable cancer cells latch on or adapt to a tissue microenvironment that is some distance away from its tumor of origin. Cancer metastasis is the process that is responsible for the spread of cancer to other parts of the body.6

Once the cancer metastasis takes place, surgery for removing the tumor will no longer be an effective treatment since the cancer has already spread too far too many places to be removed surgically. In such cases, chemotherapy, targeted therapy, and other types of cancer medications will need to be given in order to control the now widespread growth of the cancer cells that have spread to and settled down at various places in the body. This dramatically reduces the survival rate of people who have cancer.7

Cancer Metastasis and Drug Resistance

While metastasis poses a massive problem in the effective treatment of cancer, another issue that hinders the successful treatment of cancer is drug resistance. Drug resistance happens when a targeted therapy or chemotherapy medications that have been working quite well at the start of the treatment, suddenly fails to kill the cancer cells after a certain point of time. Drug resistance is usually responsible for most of the relapses of cancer and is also one of the leading causes of cancer-related death. Due to this failure of the drug, the cancer begins to grow again and comes back after initially disappearing for some time while the treatment was going on.8, 9

Oncologists, scientists, and medical experts have all been striving to find out what exactly is the cause of metastasis and drug resistance for many decades now. As technologies in gene sequencing and other devices that allow molecular diagnosis emerge, the hidden reason behind metastasis and drug resistance is slowly being discovered.

Studies were done on cancer metastasis, also referred to as cancer invasion, and drug resistance has recently found a relationship between drug resistance and cancer metastasis. A potential association between these two phenomena has been shown by two types of scientific observation. The first being – certain tumor cells are selected for being resistant to medications, and they are more metastatic or invasive as compared to the non-resistant parental (or original) cancer cells.

The second observation is that in some instances, the secondary tumors (or the metastatic ones) are quite resistant to chemotherapy medication than the original tumor cells.10 However, some other studies did not find any relation between drug resistance and cancer metastasis, which is why more research is still needed to firmly prove any correlation between the two.11

One possibility is that treatment with some types of chemotherapy drugs are able to promote and enhance the phenomenon of cancer metastasis. Nevertheless, the very event of cancer metastasis itself needs more investigation because of the dramatic reduction in survival rate that follows. There is no doubt that a better understanding of the exact relationship between metastasis and drug resistance would lead to more successful cancer treatments.

Conclusion

At present, strategies to deal with metastasis and drug resistance are focused on the continuous monitoring of cancer patients, even after the treatment has finished. This is done through a mix of chemotherapy and/or target drugs, which target the specific proteins that are known to be responsible for triggering the drug resistance pathways in cancer patients.

Further research is required to establish a link between metastasis and drug resistance. Already the challenges of metastasis and drug resistance are gathering tremendous attention from the medical community, and clinical trials at multiple levels are ongoing to somehow find out the connection between drug resistance and tumor metastasis. Molecular diagnosis and gene analysis tools such as the Nex-Gen sequencing (NGS), ‘liquid biopsy’, and others are being used to detect changes in tumors and how the cancer cells spread from one part of the body to the other.

Combination therapies are also becoming more popular over the use of single-drug therapy to combat drug resistance. Combination drugs that focus on multiple molecular and genetic targets are being researched to prevent the relapse of cancer and save the lives of more patients.

Finally, the most critical factor for patients to bear in mind is that the earlier a tumor is detected, the lesser will be the likelihood of drug resistance and metastasis, and the treatment will also be more successful. So, if you notice any suspicious signs and symptoms, it is always better to have it checked out by your doctor, rather than to wait and allow the cancer to spread.

References:

  1. Hoadley, K.A., Yau, C., Hinoue, T., Wolf, D.M., Lazar, A.J., Drill, E., Shen, R., Taylor, A.M., Cherniack, A.D., Thorsson, V. and Akbani, R., 2018. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell, 173(2), pp.291-304.
  2. Walsh, D., Donnelly, S. and Rybicki, L., 2000. The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Supportive care in cancer, 8(3), pp.175-179.
  3. National Cancer Institute. 2020. Cancer Statistics. [online] Available at: <https://www.cancer.gov/about-cancer/understanding/statistics> [Accessed 8 August 2020].
  4. Siegel, R.L., Miller, K.D. and Jemal, A., 2015. Cancer statistics, 2015. CA: a cancer journal for clinicians, 65(1), p.5.
  5. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A., 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), pp.394-424.
  6. Gupta, G.P. and Massagué, J., 2006. Cancer metastasis: building a framework. Cell, 127(4), pp.679-695.
  7. Poste, G. and Fidler, I.J., 1980. The pathogenesis of cancer metastasis. Nature, 283(5743), pp.139-146.
  8. Gottesman, M.M., 2002. Mechanisms of cancer drug resistance. Annual review of medicine, 53(1), pp.615-627.
  9. Holohan, C., Van Schaeybroeck, S., Longley, D.B. and Johnston, P.G., 2013. Cancer drug resistance: an evolving paradigm. Nature Reviews Cancer, 13(10), pp.714-726.
  10. Liang, Y., McDonnell, S. and Clynes, M., 2002. Examining the relationship between cancer invasion/metastasis and drug resistance. Current Cancer Drug Targets, 2(3), pp.257-277.
  11. Mashouri, L., Yousefi, H., Aref, A.R., mohammad Ahadi, A., Molaei, F. and Alahari, S.K., 2019. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Molecular cancer, 18(1), p.75.

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