PLKLFC
Prostate cancer has been one of the most commonplace diseases for humans. According to the Hong Kong Government, prostate cancer is the third most common cancer in men and the 4th most common cancer for both genders. (Cancer Online Resource Hub - Cancers in Hong Kong - Common Cancers in Hong Kong - Prostate Cancer, n.d.) This disease swept through different countries, in 2022, there were 1.47 million new cases of prostate cancer globally. Apart from the prevalence of prostate cancer, never should we overlook its lethality. The five-year survival rate for prostate cancer at stage four is merely 45%. (WCRF International, 2024) Unfortunately, a vast majority of patients do not even know that they have become a victim of prostate cancer until the later stages, due to the subtle symptoms and the high cost to receive screening. (How Much Does a Prostate Cancer Test Cost? - CostHelper, n.d.) In light of this, our team has decided to revolutionize prostate cancer treatment this year by inventing an innovative prostate cancer therapy and detection method which is far superior than our conventional alternatives, to continue our effort and passion in the oncological field in the past years.
History of prostate cancer
Since the last century, scientists have been developing ways to detect and treat prostate cancer.
Important development of treatment of prostate cancer
|
Year |
Event |
|
1904 |
Hugh Hampton Young performed the first radical prostatectomy (Denmeade & Isaacs, 2002) |
|
1945 |
Introduction of retropubic approach to prostatectomy by T. Millin (Millin, 1945) |
|
1965 |
The first prostate cancer patients treated with external beam radiotherapy (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
1968 |
Discovery of androgen receptor (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
1971 |
The method for synthesizing luteinizing hormone releasing hormone (LHRH) was discovered (Schally et al., 1971) |
|
1981 |
Scientist found out that chemotherapeutic agent, estramustine, was useful for treating prostate cancer (Quinn et al., 2017) |
|
1983 |
Introduction of a new nerve-sparing technique for radical prostatectomy by Walsh et al. (Denmeade & Isaacs, 2002) |
|
1984 |
The first LHRH analogs approved for commercial use in prostate cancer (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
1989 |
Cyproterone (antiandrogen) acetate was approved by the FDA for the treatment of prostate cancer (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
1996 |
New chemotherapeutic, mitoxantrone, was introduced to treat mCRPC (metastatic castration-resistant prostate cancer) (Tannock et al., 1996b) |
|
2003 |
Abarelix, the first LHRH antagonist was approved by FDA (Moul, 2014) |
|
2004-2022 |
Several drugs were being tested and developed (Lehtonen & Kellokumpu-Lehtinen, 2023) |
Important development of diagnosis of prostate cancer
|
1938 |
Discovery of first useful biomarker in prostate cancer diagnosis: Prostate-specific acid phosphate (PAP) (Gutman & Gutman, 1938 ; Kong & Byun, 2013b) |
|
1966 |
Publication of Gleason histopathological grading system by Donal F. Gleason, which gradually replaced the preceding Broders classification system from 1926 (Epstein, 2018 ; Kweldam et al., 2018) |
|
1973 |
Introduction of MRI imaging by Paul Lauterbur, Nobel laureate of 2003 (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
1979 |
Discovery of PSA (Rao et al., 2007 ; Wang et al., 1979) |
|
1987 |
Stamey et al. find out that PSA is a useful biomarker in prostate cancer. (Stamey et al., 1987c) |
|
1987 |
Discovery of PSMA by Horoszewicz et al. in the LNCaP cell line. (Horoszewicz et al., 1987) |
|
1989 |
Introduction of systematic biopsy technique by Hodge et al. (Hodge et al., 1989) |
|
1991 |
Catalona et al. first demonstrated that the PSA blood test could be used as a first-line screening test for prostate cancer (Catalona et al., 1991) |
|
2005 |
The ISUP decided that Gleason scores below 5 should not be used, its use gradually declined (Epstein et al., 2005) |
|
2010s |
The performance of MRI prior to biopsy to reduce the number of needless biopsies (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
2012 |
PSMA PET/CT scans has started to be performed (Lehtonen & Kellokumpu-Lehtinen, 2023) |
|
2012 |
The European Society of Urogenital Radiology (ESUR) released a version of the PI-RADS® classification system for prostate MRI lesions (Barentsz et al., 2012) |
|
2014 |
ISUP conference proposed a new classification system, which reclassified Gleason scores 6-10 into corresponding ISUP grade groups 1-5 (Epstein et al., 2016) |
Prostate cancer is the fourth most common cancer in Hong Kong and the fourth most common cancer in the world (WCRF International, 2024), affecting one in seven men. Currently, there are a few ways to detect prostate cancer.
|
Method |
Prostate-specific antigen (PSA) blood test |
Digital rectal examination (DRE) |
Fine Needle biopsy |
|
Description |
It is a blood test that detects prostate cancer by measuring the amount of PSA in the blood A high level of PSA in the patient’s blood may indicate certain abnormalities, including prostate cancer. (Prostate-Specific Antigen (PSA) Test, 2022) |
The doctor will insert a gloved and lubricated finger into the patient’s rectum to feel for any bumps or hard areas on the prostate, which may be a sign of prostate cancer (Prostate Cancer Screening; Digital Rectal Examination, n.d.) |
It is a procedure to remove a piece of tissue or a sample of cells from the prostate It inserts a special needle through the skin to collect cells from a suspicious area The specimen will be analyzed in a laboratory to determine whether cancer cells are present (How Much Does a Prostate Biopsy Cost?, n.d.) |
|
Advantages |
(Prostate-Specific Antigen (PSA) Test, 2022) |
(Ying et al., 2023) |
|
|
Disadvantages |
(Prostate-Specific Antigen (PSA) Test, 2022) |
(Prostate Cancer Screening; Digital Rectal Examination, n.d.) |
(Prostate Cancer Screenings | Misleading Results | Vista Urology, n.d.) |
|
Accuracy |
Around 25% (Prostate-Specific Antigen (PSA) Test, 2022) |
Around 63% (Ying et al., 2023) |
Around 82% (Narayan et al., 1989) with a false negative rate of 30%-40% |
|
Cost |
At-home:USD $20-$50 At-hospital:USD$120 or more (How Much Does a Prostate Cancer Test Cost? - CostHelper, n.d.-b) |
USD $551 (Prostate Cancer Screening; Digital Rectal Examination, n.d.) |
USD $407-$2,585 (How Much Does a Prostate Biopsy Cost?, n.d.) |
Besides having different detection methods, there are also various treatments for different stages of prostate cancer.
|
Treatments |
Radical Prostatectomy |
External Beam Radiation |
Cryotherapy |
|
Description |
It removes part of the prostate or the entire prostate and some of the tissue around it It can be done through an incision made in the wall of the lower abdomen or in the perineum |
It uses high-energy beams such as X-rays or protons to kill cancer cells |
It freezes cancer cells and destroys them. |
|
Advantages |
|
|
|
|
Disadvantages |
|
|
|
|
10-year survival rate |
88.9% (Kibel et al., 2012) |
82.6% (Kibel et al., 2012) |
90.5% (Cheetham et al., 2010) |
|
Cost |
Around USD$17,226 (Burkhardt et al., 2002) |
Around USD $14,048 (Burkhardt et al., 2002) |
Around USD $11,215 (UCLA Researchers Find a Wide Variation in Costs to Treat Low-risk Prostate Cancer, 2015) |
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.
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 has inspired 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.
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 the patient’s 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 (Carpenter & Brady, 2023).
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. If Gluc protein is detected in the patient’s urine, it 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 will Gluc 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).
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
Through our product, prostate cancer patients would not need to suffer the many side effects of current treatments like radiotherapy, radical prostatectomy or chemotherapy. The side effects of these traditional treating methods include hair loss, erectile dysfunction and urinary retention, while patients using our product will only need to endure some wound pain.
Through intravenous injection, our medication can be administered anywhere, even in clinics or medical tents in less developed countries. The detection of prostate cancer will no longer be limited to hospitals, and the treatment of prostate cancer will not need to take place in an operating theatre or in a room with an enormous radiotherapy device, which is very convenient for 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 through a simple and quick reaction. The whole process only takes place for less than an hour, which is very fast when compared to the current detection methods.The strength of project is called PCAs, which is the abbreviation for prostate cancers
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.
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.
The plasmid that we are designing 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. (Tai et al., 2020). 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.
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