Prostate cancer treatment is evolving, moving towards more personalized approaches. Targeted therapy represents a development in this field, offering a method designed to act specifically against cancer cells. This form of treatment is based on the genetic characteristics of an individual’s cancer.
How Targeted Therapy Works
Targeted therapy operates on a principle of precision, distinguishing it from traditional treatments like chemotherapy. These therapies are designed to identify and attack specific molecules that are characteristic of cancer cells. This approach allows the drugs to interfere with the signals that prompt cancer cells to grow and divide, thereby halting their progression. The specificity of this method helps to limit the damage inflicted upon surrounding healthy cells.
The action of targeted therapy can be compared to a key fitting into a specific lock. The drug is the key, and a particular molecule on or within the cancer cell is the lock. Only when the key fits the lock can the drug execute its function, which is to block the cancer cell’s ability to thrive. This contrasts with chemotherapy, which affects all rapidly dividing cells, including healthy ones like those in the hair follicles and digestive tract, leading to a broader range of side effects.
These drugs circulate through the bloodstream, enabling them to reach cancer that has spread to different parts of the body. This systemic reach makes them a useful option for treating advanced stages of the disease. By focusing on the unique attributes of cancer cells, targeted therapies can be effective even when other treatments are not.
Key Molecular Targets in Prostate Cancer
The effectiveness of targeted therapy in prostate cancer hinges on identifying specific vulnerabilities within the cancer cells. These vulnerabilities are often revealed through biomarkers, which are measurable indicators of a biological state. Two primary targets have become the focus of current therapies: mutations in DNA repair pathways and the presence of specific proteins on the cell surface.
One target involves genes responsible for repairing damaged DNA, such as BRCA1 and BRCA2. In healthy cells, these genes are part of a complex system that fixes errors in the DNA sequence, maintaining cellular stability. When these genes are mutated and non-functional in cancer cells, the cells become dependent on other repair mechanisms to survive. This dependency creates a specific weakness that can be exploited.
Another target is a protein found on the surface of prostate cells called Prostate-Specific Membrane Antigen (PSMA). While PSMA is present on normal prostate cells, its levels are significantly higher on prostate cancer cells, with some studies indicating its presence in over 80% of cases. This high concentration acts like a homing beacon, allowing treatments to specifically locate and act upon the cancerous cells while largely sparing healthy tissue.
Types of Targeted Drugs Used
For prostate cancers with weaknesses in their DNA repair systems, a class of drugs known as PARP inhibitors is used. PARP (poly(ADP)-ribose polymerase) enzymes are proteins that help repair DNA. By blocking these enzymes, PARP inhibitors prevent the cancer cells from mending their DNA, which ultimately leads to cell death. This approach is particularly effective in cells that already have a faulty repair system due to mutations like those in the BRCA genes. Specific PARP inhibitors approved for use include olaparib (Lynparza) and rucaparib (Rubraca).
For cancers that exhibit high levels of Prostate-Specific Membrane Antigen (PSMA), a different approach called radioligand therapy is employed. This method can be thought of as a “smart bomb,” combining a molecule that seeks out PSMA with a radioactive particle. The targeting molecule binds to the PSMA on the surface of prostate cancer cells, delivering a precise dose of radiation directly to the tumor. Lutetium-177 vipivotide tetraxetan, marketed as Pluvicto, is a PSMA-targeted radioligand therapy approved by the FDA.
These targeted drugs are often administered as part of a broader treatment plan. PARP inhibitors, for instance, are typically given alongside hormone therapy. They are taken orally as pills or capsules, usually once or twice a day.
Patient Eligibility and Treatment Process
Determining who is a candidate for targeted therapy is a multi-step process that begins with a thorough evaluation of the cancer’s characteristics. These treatments are generally considered for patients with advanced prostate cancer that has spread (metastasized) or has become resistant to standard hormone treatments, a condition known as castration-resistant prostate cancer. The decision to use a targeted drug is not based on the stage of the cancer alone; it depends on the presence of specific molecular markers.
A central component of determining eligibility is biomarker testing. This involves analyzing a sample of the tumor tissue or a blood sample to identify specific genetic mutations or protein expressions. For a patient to be considered for a PARP inhibitor, their cancer cells must have a mutation in a DNA repair gene like BRCA1 or BRCA2. Similarly, to be eligible for PSMA-targeted radioligand therapy, a patient’s cancer cells must show high levels of PSMA, which is confirmed using a specialized imaging test called a PSMA PET scan.
As with any cancer treatment, these therapies have potential side effects. Common side effects for PARP inhibitors can include nausea, fatigue, and a low red blood cell count (anemia). Side effects are managed by the healthcare team and depend on the specific drug and the patient’s overall health.