-Project Description-

Prostate cancer is the fourth most common cancer in Hong Kong and the fourth most common cancer in the world. It affects one in seven men. Currently, there are a few ways to detect prostate cancer.

Besides having different detection methods, there are also various treatments for different stages of prostate cancer.

In this project, we are investigating a method to detect and kill prostate cancer cells in a patient's body. Our project will include two medications, one can only detect PSMA-positive cancer cells, the other one can detect and kill prostate cancer cells.

1. Medication for detecting PSMA-positive cancer cells

According to a recent research, more than 80% of patients with prostate cancer are having the symptom of high PSMA expression. (Hope et al., 2017; Minner et al., 2010) This motivates us to design a plasmid that can detect PSMA-positive prostate cancer cells in the patient’s body. Based on the recent research, PSMA is usually overexpressed in prostate cancer (Tayara et al., 2024) and it can be used to determine the aggressiveness of prostate cancer (Bravaccini et al., 2018; Minner et al., 2010). Therefore, when the plasmid is injected into the patient’s prostate gland, it is expressed and produces a fluorescent protein called gaussia luciferase (GluC). By determining the light intensity of the fluorescent protein in the patient’s urine, PSMA-positive prostate cancer cells can be detected.

2. Medication for detecting and killing prostate cancer cells

In the plasmid, there are not only genes for detecting prostate cancer, there is also a gene for killing the prostate cancer cells in advance. The gene we inserted into the plasmid will produce BAX, which is a protein that triggers apoptosis of cells. Therefore, after the plasmid is released into the cell, not only can it cause the cell to express a fluorescent protein and release it to urine for detection, it can also trigger the cell to undergo apoptosis and kill the cancer cell.

There are several components we have chosen for the whole medication: PSMA promoter, probasin promoter, GluC protein, and BAX

PSMA promoter is a promoter that will be activated only when it is located in an environment with a high PSMA level. It has transcriptional activity in PSMA(+) cell lines and no activity in PSMA(-) cell lines (Zeng et al., 2005b).

Probasin (PB) promoter is a promoter that is highly prostate specific (Lowe et al., 2001) and will only be activated when it is located in the prostate gland. It allows us to ensure the plasmid is expressed in PSMA-positive prostate cancer cells.

Gaussia luciferase, GluC, is a bioluminescent enzyme that will emit blue light with a wavelength of 480 nm under certain reactions (Tannous & Teng, 2011). It will be expressed under a high PSMA level at the prostate gland and be detected in the patient’s urine with the help of a plate reader. Using GluC in our project but not GFP, a common fluorescent protein, is because GFP is cytotoxic and will cause cell death (Ansari et al., 2016).

BAX, also known as Bcl-2-like protein 4, is a crucial component in the regulation of apoptosis, or programmed cell death. The expression of BAX by the plasmid will promote the prostate cancer cells to undergo apoptosis.

First of all, we have designed a plasmid that can detect PSMA-positive prostate cancer cells. The plasmid consists of two parts, the PSMA promoter and the gene that can express GluC. When the plasmid is located at the prostate gland, the PSMA promoter will be activated and GluC will be expressed. GluC protein will be detected in the patient’s urine, which indicates the presence of prostate cancer cells in the patient’s prostate gland.

Based on the plasmid for the detection, we have further made some changes to allow the plasmid to have another function, killing the prostate cancer cells. We have changed the promoter to probasin promoter, and added another gene that can express BAX into the plasmid. When the plasmid is expressed in the prostate gland, not only GluC will be expressed and detected by a plate reader in the patient’s urine, but BAX will also be expressed to trigger the prostate cancer cells to undergo apoptosis, which is observable in cell line by checking the cell viability (Lowe et al., 2001).

Check out for the details of the design on the experimental design page

Figure 1: Medication for detecting PSMA-Positive cancer cells

Figure 2: Medication in normal somatic cells

Figure 3: Medication for detecting and killing cancer cells

The strength of project is called PCAs, which is the abbreviation for prostate cancers

Prostate cancer patients do not need to undergo treatments like radiotherapy, radical prostatectomy or chemotherapy, which have many side effects like hair loss or wound pain. They just need to have a dosage or two to treat their cancer, which is just like injecting a vaccine.

The injection of our medication can take place anywhere, even in clinics or medical tents in the least-developed countries. The detection of prostate cancer no longer takes place in a hospital, and the treatment of prostate cancer does not need to take place in an operating theatre or in a room with an enormous radiotherapy device, which is very convenient to the patients.

The current methods for the detection of prostate cancer costs several hundred US dollars, and the cost for treatment is even much more expensive. Our medication allows prostate cancer patients to detect and kill prostate cancer cells with only a dosage or two, with each dosage costing less than a hundred US dollars. This price is affordable to most of the patients in the world, even for those who are living in less-developed countries.

Our medication allows patients to obtain the result in only a short period of time, which is mostly less than an hour. The patients can detect prostate cancer by collecting their urine after injecting the medication, and measure the light intensity of GluC in their urine by a short reaction. The whole process only takes place for less than an hour, which is very fast when compared to the current detection methods.

Killing the prostate cancer cells is also very speedy, as it only takes place after gaussia luciferase and BAX are expressed in the patient’s cancer cells. The whole process only lasts for less than an hour, which is very quick when compared to the current methods that lasts for several hours.

As we are just designing the plasmid, which is only part of the medication. In the future, we will try to develop a delivery system that can deliver the plasmid to the patient’s body through a polymer and an aptamer, which has been proposed by Tai et al. (2020b). We hope to deliver the medication to the patient’s prostate gland through intramuscular injection in the future.

Moreover, we are just simulating the fate of plasmids with a cell line, which cannot completely reveal the real effect of them in the human body. Therefore, we may try to apply the medication to mammals like rats, in order to understand the effect of plasmids on the human body more clearly.

Although inventing the medication is the major goal of our project, we also want to help prostate cancer patients as soon as possible. Therefore, our next step is to apply it to real patients. In the future, we may collaborate with universities to verify the function of our medication and apply it to real patients under the government’s approval. We may also collaborate with enterprises in order to make the medication become a real product in the market in the foreseeable future.