Introduction

Prostate cancer is one of the most commonly diagnosed cancers in men and assigned male at birth (AMAB) individuals.¹ 

Although prostate cancer is a frightening diagnosis, there are many effective treatment options available. One such option is targeted therapy which is revolutionising treatment by providing precise and effective solutions. 

You may now be wondering what targeted therapies are. These medications focus on attacking the abnormal cancer cells while sparing the healthy cells, leading to fewer side effects and better treatment outcomes for patients. 

In this article, we will take a closer look into the three most common types of targeted therapy - PARP inhibitors, androgen receptor inhibitors and immunotherapies. 

Curious to know more about how these therapies work and how they may benefit patients? Keep reading to uncover how targeted therapies are changing prostate cancer care.

What is prostate cancer?

Cancer is a disease that causes the uncontrolled growth of abnormal cells due to changes or mutations in the cell’s genetic code or DNA. These mutated cells are typically stronger and more persistent than normal cells and can grow into lumps or tumours which, if left untreated, can spread to other parts of the body like the stomach and the bone; this process is called metastasis.²

In the case of prostate cancer, this uncontrolled cell growth occurs in the prostate gland, which is a part of the male reproductive system. 

The prostate gland is a small walnut-sized organ located below the bladder and in front of the rectum in males (Figure 1). The prostate gland also surrounds the tube that carries urine from the bladder to the penis which is called the urethra. 

It is responsible for producing semen, the thick white fluid which protects, nourishes, and transports the sperm out of the body during ejaculation.³

Figure 1: Location of the prostate in the male human body and prostate with tumour.³

Some common symptoms of prostate cancer include:⁴

• Difficulty urinating
  • Finding it hard to start urination
  • Weak flow of urine
  • Frequent urination at night
• Pelvic discomfort
• Blood in urine or semen

Read more about the frequently asked questions regarding the causes, prevalence, diagnosis and risk factors of prostate cancer. 

Standard treatments for prostate cancer

Typically, traditional treatments for prostate cancer include surgery, radiation therapy and hormone therapy.

Surgery 

Surgery is one of the main treatments for prostate cancer, wherein a procedure called a prostatectomy is conducted, this usually involves the removal of the prostate, and it is typically done in patients with cancer that has not spread to other body parts.^5,6 

Like any other surgery, the removal of the prostate is major surgery and carries the risk of developing serious infections, urinary incontinence (loss of bladder control and urine leakage issues), and erectile dysfunction (inability to get or maintain an erection during sexual intercourse).⁷

Radiation therapy 

Radiation therapy or radiotherapy involves the use of high-energy radiation beams like X-rays to kill cancer cells.^5,8

There are several types of radiation therapy strategies, for example, external-beam radiation therapy where a machine outside of the body is used to deliver the beams to the site of the cancer. 

Another example is brachytherapy (internal radiation therapy), where needles containing the radioactive substance are inserted through the skin between the scrotum and rectum. 

However, there are many side effects such as fatigue, urinary issues, sexual dysfunction and diarrhoea which are associated with radiation therapy. 

Hormone therapy

Hormone therapy involves stopping the production of specific hormones, which are chemicals made by glands in the body, these hormones are released into the bloodstream and carry various messages throughout the body, this aims to stop the growth of cancer cells.⁵

In prostate cancer, male sex hormones such as testosterone can cause the growth of prostate cancer tumours, hormone therapy includes a whole host of drugs like anti-androgen drugs such as flutamide and enzalutamide, these can reduce the production of testosterone in the body and reduce the growth of the cancer.^5,9 

However, there are many side effects such as fatigue, low sex drive, and hot flashes.¹⁰

What is targeted therapy?

Targeted therapies are a type of cancer treatment that “targets” cancer cells specifically by focusing on attacking or blocking specific molecular pathways that allow cancer cells to grow. Targeted therapies aim to identify and exploit the differences between healthy cells and cancer cells, such as genetic changes or mutations.¹¹

The rationale behind targeted therapies is quite simple yet ingenious, instead of affecting the whole body, targeted therapies focus on attacking the driving forces of cancer cells, in essence, exploiting the key weaknesses observed in cancer cells, like a woodpecker which focuses and keeps pecking at certain points on a tree.¹¹ 

Targeted therapies differ from traditional therapies like chemotherapy and radiotherapy (which affect both healthy and cancerous cells). Targeted therapies can be compared to using a magnifying glass to focus sunlight on a small, specific area in order to shine a light, whereas chemotherapy can be analogous to shining a large lamp to light up a room, where the area of focus is widespread. In this way, targeted therapies can often cause fewer side effects as they are precise and only focus on certain harmful cells while aiming to spare the healthy unaffected cells. 

Targeted therapies are part of a broader movement toward precision or personalised medicine where each individual’s genetic makeup and the individual characteristics of their cancers are taken into account in order to formulate the most effective treatment strategy. 

Types of targeted therapies for prostate cancer

When it comes to the treatment of prostate cancer, targeted therapies are paving the way for more personalised and effective treatment regimes. Prostate cancer can also benefit from targeted therapy, which comes in a variety of forms; let us now look at the most important ones.

PARP inhibitors

PARP (poly(ADP)-ribose polymerase) inhibitors are a kind of targeted medication that function by inhibiting the action of the PARP enzyme, which is required by certain cancer cells to repair damaged DNA. Therefore, as their name suggests, PARP inhibitors “inhibit” the functioning of the PARP enzyme, as cancer cells are unable to fix their DNA and therefore they eventually die and this leads to a reduction in the tumour.¹²

PARP inhibitors are typically prescribed to individuals with advanced prostate cancer and those who have a specific genetic mutation such a BRCA1 (BReast CAncer gene 1) or BRCA2 mutation (BReast CAncer gene 2).¹³ The presence of this particular mutation results in increased sensitivity to PARP inhibitors, meaning that if a patient had this BRCA1 or BRCA2 mutations, the efficacy of PARP inhibitors is increased. 

Olaparib and Rucaparib are two popular examples of PARP inhibitors that have demonstrated efficacy in treating cancers with these particular genetic profiles. PARP inhibitors have offered men with new hopes of recovery in cases where traditional treatments may not have worked as well. However, common side effects include exhaustion, nausea, and anaemia which may vary in intensity depending on the individual.¹⁴ 

PSMA-targeted radionuclides

PSMA (Prostate-Specific Membrane Antigen)-targeted radionuclides is a novel therapy that targets and treats prostate cancer cells by using radioactive materials. A radionuclide or a radioisotope is a small unstable chemical element which releases radiation when it breaks down. 

PSMA-targeted-radionuclides is a form of targeted internal radiotherapy and works by attaching to the PSMA protein which is abundant on the surface of prostate cancer cells. After the PSMA-targeted-radionuclides attaches to the PSMA protein, the radioactive particles are precisely delivered to the cancer cells, where the radiation can destroy the cells while simultaneously causing the least amount of harm to the surrounding healthy tissue.¹⁵

The action of PSMA-targeted-radionuclides can be compared to shooting a single microscopic ray or radiation directly to the affected areas rather than a large laser beam which estimates the generalised area of the tumour and can affect nearby healthy tissue too.

PSMA-targeted radionuclides are usually used for men with advanced or metastatic prostate cancer especially when the cancer has progressed outside the prostate and traditional treatments are no longer working. They are particularly helpful for tumours with a higher number of PSMA proteins.

For example Lu-177-PSMA, this drug delivers targeted radiation to PSMA-positive prostate cancer cells.¹⁵ However, some patients may experience side effects like dry mouth, nausea, or fatigue.

Immunotherapy in prostate cancer

Immunotherapy uses the body's own defences against cancer. Immunotherapy boosts the immune system to make it more capable of identifying and combating cancer cells, as opposed to directly attacking cancer cells with chemotherapy or radiation.¹²

Immunotherapy is used for advanced or metastatic prostate cancer that has not responded to traditional conventional treatment strategies. 

There are different types of immunotherapy used for prostate cancer, including angiogenesis inhibitors and immune checkpoint inhibitors.

• Angiogenesis Inhibitors: These medications stop cancers from growing new blood vessels, which is essential for them to grow. These inhibitors stop the cancer cell’s blood supply and prevent oxygen and nutrition from reaching the tumour and hence cause it to die¹⁶
  • Drugs like bevacizumab are being studied for their potential to inhibit blood vessel growth in tumours, although there are currently mixed results¹⁷
• Immune Checkpoint Inhibitors: these drugs stop the proteins that normally prevent immune cells from attacking cancer cells. These checkpoint proteins can be inhibited to improve the immune system's capacity to identify and combat cancer cells¹⁸
  • Drugs like Pembrolizumab are used to help the immune system fight cancer more effectively¹⁹

Although immunotherapy shows promise in prostate cancer care, it may cause side effects such as skin rashes, exhaustion, or more serious immune-related side effects, such as the immune system attacking healthy tissues.²⁰

Benefits and challenges of targeted therapies

Targeted therapies are made to specifically attack cancer cells while leaving healthy cells alive which usually leads to fewer side effects compared to traditional treatments like chemotherapy, and especially for patients with specific genetic mutation, a focused approach can result in more successful treatment outcomes. 

Moreover, in the same way that a tailor can sew clothes that match the user’s dimensions, and body shape, targeted therapies can be customised to mould each patient’s cancer, which can really offer them a more personalised treatment plan. 

On the other hand, not all patients will benefit from every targeted therapy as not all patients have specific genetic mutations, so targeted therapies can’t target anything in particular. They can also be expensive and therefore may not be easily financially accessible to everyone. Also, these treatments may eventually cause cancer cells to become resistant to them, this means that the targeted therapies no longer work as effectively as the cancer cells get used to the medication which reduces their long-term efficacy.²¹

Overall, targeted medicines are a big step forward in the treatment of prostate cancer, but getting past these obstacles will need more research and proper patient selection.

Summary

• Prostate Cancer Overview: Prostate cancer is a common cancer in men. The disease has various treatment options based on the stage and nature of the disease
• Targeted Therapies: These treatments are a form of precision medicine and aim to precisely target cancer cells with fewer side effects than traditional treatments like chemotherapy
• Key Types of Targeted Therapies:
  • PARP Inhibitors: Block function of PARP enzymes and prevent DNA repair in cancer cells. Effective in patients with specific genetic mutations (e.g., BRCA)
  • PSMA-targeted radionuclides: Delivers targeted radiation directly to prostate cancer cells by binding to a specific protein on their surface
  • Immunotherapy: Boosts the immune system to fight cancer, especially effective in certain genetic profiles

• Benefits of targeted therapies: They precisely target cancer cells and reduces damage to healthy tissue; and personalised treatment tailored to individual cancer characteristics
• Challenges of targeted therapies: They are not applicable or effective for all patients. They can be very expensive and inaccessible, resistance may develop, which limits efficacy