February 4 was World Cancer Day and here at Partners4Access, we are having a look back at how cancer treatments have evolved through the years and where they are likely to go in the future.
First came surgery
In the 18th century, surgery was hailed as the first effective cancer treatment. The discovery of anesthesia in the 19th century resulted in a further boom in surgical innovation. However, surgery had limited effect on tumor recurrence, so alternative treatments were urgently needed. Radiotherapy addressed this problem in 1896, by destroying DNA in all cancerous cells faster than healthy cells. But this therapy was extremely harsh and resulted in severe side effects, including the development of other cancers.
Chemo and combinations
In the 1940’s the first anti-cancer drugs were introduced. Nitrogen mustard, a poison gas well known for its use in the First World War, was the first licensed chemotherapy agent, and it was used to destroy lymphocytes in lymphoma patients.
After this discovery, many other chemotherapy agents were identified in quick succession. One such discovery came after patients receiving folic acid were seen to deteriorate, leading to the development of the antifolate called aminopterin. This was widely used for many years, but it was eventually discontinued due to serious side effects and replaced by methotrexate, a drug still used today.
Following the chemotherapy boom, the use of combination therapies developed into one of the most common practices in chemotherapeutic regimens, and is still a staple to this day. However, one of the biggest advancements came with the advent of adjuvant therapy, most commonly the combination of chemotherapy or radiotherapy with surgery, a much more effective weapon than any seen previously against most types of cancer.
The rise of immuno-oncology drugs
Many different targeted therapies have now been developed, such as Rituxan (rituximab), the first approved cancer drug to target monoclonal antibodies (1997), and Herceptin (trastuzumab), which followed swiftly in 1998. Then came Glivec (imatinib) in 2001, which works by inhibiting tumor signaling pathways, and Avastin (bevacizumab) in 2004, which inhibits the formation of blood vessels by tumors.
The latest and most promising new cancer therapies are those that target the PD-1 checkpoint to inhibit tumor cell proliferation. These include Keytruda (pembrolizumab), Opdivo (nivolumab) and Tecentriq (atezolizumab).
Whilst the PD-1 inhibitors are effective and have a relatively good safety profile, advancements in this field are still needed with stomach, brain, esophageal, lung and pancreatic cancers having a 10- year survival rate of under 20%.
The expansion of rare oncology
Rare cancers account for 22% of all known cancers, with over 198 identified globally. Although orphan oncology drugs are being approved at a faster rate than ever, with special programs being developed to accommodate rare diseases, there is still a huge unmet need. The first approved drug to treat a rare cancer was pentamidine isethionate for pneumocystis carinii pneumonia, in October 1984. Since then, 177 orphan drugs have been approved by the U.S. Food and Drug Administration for rare cancers, and the rare oncology space is expected to grow even more in the future.
So, what’s next for cancer treatments?
CAR therapy, in which a patient’s own T cells are modified to bind to known cancer proteins, has recently been showing promise for blood cancers like B cell acute lymphoblastic leukemia and may provide an answer to solid tumors in the future.
Understanding of epigenetics has been increasing over the last few years, with increased knowledge of how external mechanisms affecting the DNA structure can result in cancer. This has led to multiple clinical trials targeting epigenetic enzymes which regulate a cell’s genetic programming. The aim of these therapies is to revert cancerous cells back to normal ones, rather than killing them.
Finally, precision medicine may be a viable option in the future, with the cost of genome sequencing decreasing every year and programs like the 100,000 Genomes Project underway in the U.K. Increasing access to individual gene markers can be used to reverse specific gene mutations that cause cancer, with lower side effects than other therapies.
While the number of patients living with cancer has increased by almost half a million from 2010 to 2015, with an expected increase to 4 million by 2030 in the UK alone, hope is not lost. Progress in developing cancer treatments is slow but steady, with more and more funding being generated for research and drug discovery, and novel treatments being developed each year.
Evolution of cancer treatments:
Author: Joanna Fernandes, Analyst
Email Joanna at [email protected]
References
Raconteur. (2018). History of cancer treatment timeline – raconteur.net. [online] Available at: https://www.raconteur.net/healthcare/history-of-cancer-treatment
Cancer Research UK. (2018). Cancer survival for common cancers. [online] Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/survival/common-cancers-compared#heading-Zero
Macmillan.org.uk. (2018). Cite a Website – Cite This For Me. [online] Available at: https://www.macmillan.org.uk/_images/cancer-statistics-factsheet_tcm9-260514.pdf
Mskcc.org. (2018). The Future of Cancer Research: Five Reasons for Optimism | Memorial Sloan Kettering Cancer Center. [online] Available at: https://www.mskcc.org/blog/future-five-reasons-optimism
Stockklausner, C., Lampert, A., Hoffmann, G. and Ries, M. (2016). Novel Treatments for Rare Cancers: The U.S. Orphan Drug Act Is Delivering—A Cross-Sectional Analysis. The Oncologist, 21(4), pp.487-493
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