Exploring new frontiers in prostate cancer therapy
Prostate cancer is the second most common cancer in men: One out of eight men will get this diagnosis during their lifetime. It is also a topic surrounded by misconception, including the belief that only older men are at risk, and that it is always a slow-growing cancer that doesn’t require treatment. In reality, the risk of developing prostate cancer varies with age, ethnicity and other factors — each diagnosis is different.
The course of the disease and the prognosis can also vary significantly, which is why understanding the facts about prostate cancer is crucial for early detection and effective treatment.
"Metastatic prostate cancer has currently the highest unmet medical need," says Teresa Cascella, clinical development lead in Oncology at Bristol Myers Squibb in Boudry, Switzerland. "Patients with metastatic prostate cancer have a five-year survival rate of just 32%, which highlights the ongoing urgency to invest in clinical research and seek novel treatment options for patients."
Video transcript
It is projected that new cases of prostate cancer will rise from 1.4 million in 2020 to 2.9 million, uh, in 2040.
My name is Teresa Cascella and I am a Medical Doctor. I am Italian and work as a clinical development lead at Bristol Myers Squibb in Boudry, Switzerland. I trained as a physician and have always had a big passion for research, which I started at the age of 20. I conducted basic, clinical and translational research.
The main reason I decided to leave the bench and the bedside of the patient is that by joining BMS, I would have the opportunity to impact more patients. The foundation of prostate cancer treatment is ARPI (Androgen Receptor Pathway Inhibitor).
The androgen receptor is a protein, and my team and I are working on a novel technology that aims to degrade this protein. Degrading this protein means removing it from the cancer cell and to block the growth of the tumor. Despite the availability of multiple treatments for patients with prostate cancer, still, one out of three patients diagnosed with metastatic prostate cancer who have developed resistance to initial hormonal therapy, are expected to die within five years due to this disease.
The main driver for the growth of prostate cancer is the activity of testosterone on the androgen receptor. That's why the currently available hormonal therapies for prostate cancer specifically target the androgen receptor pathway. What I am most proud of is the commitment and passion of my team, which is a group of extremely talented people spread across the world, who share a single mission: Bringing innovative treatments to patients.
Because, for each of us, cancer treatment is personal.
Prostate cancer research has progressed significantly over the last several years, with many new treatments established as standards of care, including hormone and radioligand therapy and immunotherapy. A special research focus is Metastatic Castration-Resistant Prostate Cancer (mCRPC), where the standard of care and many existing therapies are currently reaching their limits. Oftentimes, these cancer cells continue to grow and spread, despite being "starved" by hormone therapy.
The intriguing science of degrading a protein
To potentially expand the range of treatment options and improve the prognosis for mCRPC patients who have exhausted other forms of treatment, great hopes are placed on so-called protein degraders. The science behind them is intriguing: human cells constantly produce and break down proteins as part of their normal functions, but sometimes that process doesn’t go as expected, and the accumulation of certain proteins can lead to diseases like cancer or autoimmune conditions. Targeted protein degradation seeks to help prevent this accumulation. It employs degraders — molecules that bind to proteins needed by cancer cells. Once in place, these degrader molecules send a signal to the cell’s machinery to dismantle the cancer-promoting proteins so they’re no longer functional.
"One of the main drivers for tumor growth in prostate cancer is a specific receptor pathway that regulates the activity of testosterone," explains Teresa. "Currently available hormone therapies block or reduce the activity of the receptor pathway. A new mode of action currently being investigated aims to tackle the receptor — which is a protein — in a different way, by degrading it. In this way, it may help deprive the tumor of its growth basis and overcome the resistance issues current hormone therapies have."
What’s next?
Beyond prostate cancer and building on our legacy and scientific expertise, BMS is at the forefront of discovering and developing novel degraders in therapeutic areas with high unmet need that specifically target disease-causing proteins. A targeted protein degradation platform provides an innovative way to tap into targets that are driving diseases that were previously considered undruggable.
Video transcript:
Cells need the right kind and amount of proteins to work properly. When a cell accumulates too many proteins, it must find a way to get rid of them.
Like a sorting machine at a recycling plant, cells have built-in mechanisms to look for any damaged or excess proteins.
If the protein meets either of these criteria, the cell can "tag" the protein with a signaling protein called ubiquitin.
The ubiquitin protein tag signals that the unwanted protein is ready to be broken down by specialized internal cellular machinery called proteasomes.
The proteasomes break down and recycle the no longer needed protein into fundamental raw materials, including amino acids, which can then be reused by the cell to build new proteins.
Bristol Myers Squibb is using this knowledge to advance innovative science and bring transformational therapies to patients.Cells need the right kind and amount of proteins to work properly. When a cell accumulates too many proteins, it must find a way to get rid of them.
Like a sorting machine at a recycling plant, cells have built-in mechanisms to look for any damaged or excess proteins.
If the protein meets either of these criteria, the cell can "tag" the protein with a signaling protein called ubiquitin.
The ubiquitin protein tag signals that the unwanted protein is ready to be broken down by specialized internal cellular machinery called proteasomes.
The proteasomes break down and recycle the no longer needed protein into fundamental raw materials, including amino acids, which can then be reused by the cell to build new proteins.
Bristol Myers Squibb is using this knowledge to advance innovative science and bring transformational therapies to patients.
Another important focus is on the development of novel technologies that have the potential to safely deliver medicines via alternative routes of administration, to potentially make arduous therapies easier for patients.
"We are also continuously improving our knowledge of tumor biology, whether it is through genomic profiling, biomarkers, or examining other correlative data from previous studies," says Teresa. "It is truly exciting science, and I am proud of the commitment of the people I work with. For each of us, cancer treatment is personal."
Subscribe to Our stories alerts
Beyond just relevant information about Bristol Myers Squibb's therapeutic areas and innovation, Our stories offer a window into the work our employees do every day for patients.
- Cancer,
- Cancer Research,
- Science & Innovation