Accelerating innovation in the US
A review of the funding and knowledge gaps in prostate cancer research across the US: 2024
What we still don’t know about prostate cancer
Key knowledge gaps
We need to screen for prostate cancer but current tests aren’t good enough
Traditional ways to detect prostate cancer include the prostate-specific antigen (PSA) blood test, a biopsy, and digital rectal examination (DRE). The PSA test is controversial as there are questions over its accuracy – with 3 in 4 men with high PSA not having cancer, and 1 in 7 aggressive cancers could be missed by the PSA test. The large PLCO (Prostate, Lungs, Colon and Ovarian) cancer trial found that there was no difference in the rate of death between people who received Annual PSA and DRE testing and the control group. A medical professional conducting a DRE can only feel one part of the prostate, so it’s limited in its ability to detect cancer and many men find it unpleasant, invasive and embarrassing. While MRI makes diagnosis more accurate, many centres can’t offer it and patients can’t access it.
We need to tackle overdiagnosis and overtreatment
Current diagnostics may lead to the diagnosis of many prostate cancers that are unlikely to cause harm to the patient. Overdiagnosis can lead to the prescription of medications the patient does not need, unnecessary stress and anxiety, financial costs, and the patient living with side effects they simply never needed to experience, including exhaustion, erectile dysfunction, and urinary incontinence.
We need to dig into diet and exercise
Men in Western countries tend to consume high-fat diets that are low in vegetables, while pursuing an inactive lifestyle. As such, they are more prone to obesity. At present, we don't know enough about how this may contribute to their prostate-cancer risk. Regular exercise increases the survival rates of people at high risk of developing prostate cancer and helps men cope with the side effects of their treatment. If we knew more about the role of diet and exercise in cancer we could save and improve many more lives.
Meddling microbiomes
The human body has trillions of microbial cells. They and the genes they bear make up the microbiome. Changes in gut microbial activity influence the risk of various cancers such as colon, liver, pancreas and many more, and we now know that there’s a correlation between prostate cancer development and microbial communities within the host but there is a lack of in-depth understanding of this mechanism in prostate cancer.
Taming tumour heterogeneity
One of the greatest challenges in treating prostate cancer is how different one person’s prostate cancer is from someone else’s. A better understanding of tumour heterogeneity would help us to tame more cancers.
Perfecting prostatectomy
Performing prostate cancer surgery, also known as prostatectomy, is one of the curative options to remove the prostate cancer tumour. However, the major concerns around prostate cancer surgery are incomplete resection and under-staging of metastatic cancer, which could result in disease recurrence. Complete removal of the prostate gland may remove the primary tumour but could potentially damage the surrounding nerves, causing adverse effects such as urinary incontinence and erectile dysfunction.
Resisting resistance
Many prostate cancers still become resistant to current therapies, by a wide variety of mechanisms, some better understood than others.
Breaking bone metastasis
Bone metastasis is the main cause of death in advanced prostate cancer, with prostate cancer predominantly spreading to the ribs, thoracic, ilium of the pelvis and lumbar vertebrae. Bone metastasis not only shortens life, it also leads to profound pain, bone fractures, spinal cord compression, neurological deficits, and the release of dangerous levels of calcium into the blood. We have very few treatment options once cancer reaches the bone and most patients on these treatments relapse.
New emerging targets
The use of AI with MRI in both lesion detection and lesion classification
One of the great challenges in prostate cancer diagnosis and its subsequent treatment is that current ways of diagnosing prostate cancer are not accurate enough, or tell us enough about how the cancer is likely to behave in future. The use of AI-powered techniques, in conjunction with MRI, could improve diagnosis and reduce overtreatment by being able to diagnose prostate cancer more accurately, including, potentially, the difference between tumours which need to be treated and those which don’t.
Complex changes that happen in the tumour microenvironment to promote disease severity, metastasis, and drug resistance
It’s clear that we haven’t fully exploited the area around the tumour. This is called the tumour microenvironment and is a complex structure containing, for example, blood vessels and components of the immune system. We now know that changes in the microenvironment play a pivotal role prostate cancer, but the complex changes that happen in the microenvironment to promote disease severity, metastasis, and drug resistance aren’t yet fully understood. We also don't know how to best rein in the tumour by harnessing the area around it.
AR new targets in a well-known pathway
While the androgen receptor’s central role in prostate cancer is well known and the target of countless interventions, recent studies have sparked interest in the role of AR signalling in macrophages in the prostate stroma.
Calcium signalling in prostate cancer
Calcium signalling is one of the key mechanisms that controls how our cells work. The progression of prostate cancer to an advanced form involves changes in calcium signalling, suggesting that tackling calcium dynamics in cancer is a potential targeted therapeutic strategy in the future.
Maximising the impact of microRNAs
MicroRNAs play a crucial role in cancer development and new evidence suggests some microRNAs could act as a novel biomarker and therapeutic target for bone metastatic prostate cancer.
Radical Radioligands
The past few years have seen an explosion of interest in radioligands, which are tiny particles in which a radioactive treatment (“radio”) is attached to something that is capable of tracking down a cancer cell (“ligand”). For example, PSMA is a protein found in more than 90% of prostate cancers which can be used to successfully guide radioactive treatments and diagnostics to them. Radioglands are being explored in several innovative new ways to help patients. One approach involves making surgeries safer and reducing side effects. For example, PSMA ligands like technetium-99 (99mTC) and indium-111 (111-In) are being used as tracers in radio-guided surgeries, including robot-assisted procedures. Another promising development is the use of Actinium-225-labeled PSMA (225Ac-PSMA). This novel radioligand is showing potential as a safe therapeutic option for metastatic prostate cancer that no longer responds to hormone therapy.
