Team:ETH Zurich/Background
Background
Introduction
In 2015, cancer claimed the lives of 8.8 million people and still remains the second leading cause of death. The majority of these cases are due to cancers originating from malignant solid tumors - tumors developing in solid tissues such as breast and liver. In 2013, WHO launched the Global Action Plan for the Prevention and Control of NCDs 2013-2020, aiming at reducing the global mortality due to diseases such as cancer by 25% by 2020. To fulfil this goal, safe and effective treatment options are required. [1]
Current Approaches to Treating Cancer
Today, there are several approaches to treating cancer and in general, they can be divided into two main groups: local and systemic treatment options. Local treatment options include surgery and radiation therapy, while systemic options refer to chemotherapy, targeted therapy and immunotherapy. Typically, the patient will receive a combination of different treatments extended over several weeks to months. [1]
Surgery
Surgery is a local treatment modality that includes removal of the visible tumorous tissue along with a margin of healthy tissue of a variable size.
- usually a one time procedure
- well established
- great for large and isolated solid tumors
- locally invasive and damaging
- can be contraindicated in patients with comorbidities (e.g. older patients with cardiovascular diseases might be unable to undergo anesthesia)
- not available for all sites
- not suitable for curing a metastatic disease
- can't guarantee the removal of invisible "micrometastases" in the vicinity of the primary tumor site
- can be difficult to repeat if initial procedure fails
Radiotherapy
Radiotherapy includes using ionizing radiation to cause lethal mutations in cancer cells. It relies on the fact that normal tissue repairs damage faster and more efficiently than cancerous tissue.
- not locally invasive
- includes a large safety margin to ensure destruction of micrometastatic spreading
- conventional regimen takes several weeks to complete
- normal tissue between the skin and the tumor is always affected
- long-term mutagenic and carcinogenic effects (that are stochastic and therefore do no depend on the dose)
- short-term acute damages
Chemotherapy
Chemotherapy is the treatment of cancer with conventional anti-cancer drugs. Typically, these are not specifically targeted, but tend to inflict more severe damage to rapidly-dividing cells.
- systemic treatment that can destroy all cancer cells in the body
- cheap
- dose and therefore efficiency of killing limited by severe systemic side effects due to lack of targeting
- usually involves several treatments extended over weeks or months
Targeted Therapy
Targeted therapy involves a group of drugs that are more specific than typical chemotherapeutics. It includes small molecules that target mutations in cancer cells that let them grow, divide and spread.
- in theory, only damaging to the tumor and not the healthy tissue
- requires a specific, ideal target and currently, these are unknown for most of the tumors
- systemic side effects still occuring
Immunotherapy
Immunotherapy is one of the most recent approaches to treating cancer and involves helping the patient's own immune system to fight the tumor through different strategies. CAR-T cells, the most promising form of immunotherapy, involve genetically engineering patient's own immune cells to target individual cancers specifically
- tailored to an individual
- potentially offering long lasting protection against the cancer
- autologous (patient-derived) cells and therefore not immunogenic
- specific for the cancer and can avoid normal tissue
- unpredictable systemic side effects seen in clinical trials
- specific targets/antigens still need to be found for every type of tumor, especially for solid tumors
- expensive
- complicated to produce
Our Approach
Some of the therapeutic options mentioned above are well established and have been used for decades, while others represent pioneering treatments developed thanks to advances in biological engineering. However, as seen from the list of pros and cons, no strategy is perfect. Therefore, complete removal of cancer without inflicting damage on the healthy tissue remains a challenge. [2]
To tackle this problem, we decided to look beyond these classical approaches and from the point of view of a synthetic biologist. Our search led us to the concept of bacterial cancer therapy - a strategy for treating cancer that actually dates back to the beginning of the 20th century but has since changed significantly. In the beginnings, different species of unmodified bacteria were given intravenously to cancer patients and were shown to accumulate preferentially in the tumorous tissue. This attractive inherent feature has been investigated since and is thought to be due to a combination of mechanisms, including:
- entrapment of bacteria in the chaotic vasculature of the tumor,
- production of chemotactic agents in the tumor microenvironment and
- protection from the immune system that the microenvironment, as an immuno-privileged site, offers.
Although native cytotoxicity of the bacteria was shown to inhibit tumor growth to a certain extent, simply administering unchanged bacteria intravenously has been connected to severe side effects and limited efficacy. To overcome this, engineering efforts have been made and different modifications have been implemented and are currently being tested in clinical trials. However, full potential of bacteria as an anti-cancer agent has not yet been fulfilled. [3]
To find out how we envisioned to take advantage of what bacterial cancer therapy potentially offers, go to our project description.
References
- ^ "Types of cancer treatment." cancer.gov. National Cancer Institute, 6 Apr. 2017. Web. 30 May 2017.
- ^ Miller, Kimberly D., et al. "Cancer treatment and survivorship statistics, 2016." CA: a cancer journal for clinicians 66.4 (2016): 271-289.
- ^ Forbes, Neil S. "Engineering the perfect (bacterial) cancer therapy." Nature reviews. Cancer 10.11 (2010): 785.
