Nav: Home

Colorado study suggests new strategies against bone metastases from prostate cancer

December 02, 2019

When prostate cancer spreads, it most often spreads to bone. And while the 5-year survival rate for prostate cancer that has not spread is nearly 100 percent, once the disease reaches bone, the 5-year survival rate is only 29 percent. Now a University of Colorado Cancer Center study published in the Journal for Immunotherapy of Cancer suggests a new approach, or, possibly two new approaches against these bone metastases: While targeted therapies and anti-cancer immunotherapies have not been especially successful against primary prostate cancers, the study suggests that both these approaches may be effective against the bone metastases that grow from primary prostate cancers, and, in fact, the type of bone metastasis may dictate which targeted therapies and immunotherapies work best.

There are two types of bone disease from metastases: lytic metastases, which destroy bone tissue, and blastic metastases, which build new bone-like tissue with cancer cells. Currently, it doesn't matter if a bone metastasis is lytic or blastic - they are both treated the same way. But the current study shows that the genetic and cellular landscapes of these two types of metastases are different, providing different drug targets and suggesting different treatments.

"The genetic and immune checkpoint changes are like those seen in other solid tumors, making it potentially possible to apply new strategies to prostate cancer patients with metastatic bone disease," says paper first author Claire Ihle, PhD student in the lab of CU Cancer Center investigator and paper senior author Philip Owens, PhD.

Lytic metastases were characterized by over-activity in a genetic signal called pAKT and its larger signaling pathway called PI3K-AKT, both of which have been targets for drug development in other cancers. Meanwhile, blastic lesions had over-activity in another genetic signal called pSTAT3 and its signaling pathway JAK-STAT, for which FDA-approved drugs already exist.

"I was really shocked by the increase in pSTAT3 in the blastic patients. I expected that these bone-producing (blastic) lesions would have little to no specific targets. I am glad I was wrong as these are the most common lesions in prostate cancer patients," Ihle says. "I would love to see STAT3 inhibitors go to blastic-type patients if we have more data showing a good response."

Importantly, both types of bone metastases also had characteristics that predict response to immunotherapy. Doctors and researchers call primary prostate cancers "cold," meaning they tend not to provoke an immune response. However, both blastic and lytic bone metastases had high levels of the protein PD-L1, which could mean they are more likely to respond to the class of anti-cancer immunotherapy known as checkpoint inhibitors.

"The other interesting point of our studies is that we developed a test that can directly measure immunotherapy and pathway targets in bone metastases," Owens says. "This is significant because we could potentially use this as a test to determine which of the many immunotherapies could be best for an individual patient, one at time, and truly provide a personalized therapy. If I had metastatic disease in bones, I would like a pathology department to know that the immunotherapy they wish to treat me with has a good level of target in the tissue they are hoping to treat."

The group is now focused on testing therapies in mouse models of lytic and blastic bone metastases to determine the most promising drugs and drug combinations.

"The pathway-targeted therapies could be used in combination with immunotherapy or alone and we really don't know if or how to combine them," Owens says.

Previously, the field assumed that bone metastases could be treated the same as the primary prostate cancers from which they grow. Now, the current study shows that's not the case, and even pinpoints signaling pathways and immunologic weaknesses of various types of metastases. If these findings stand the test of ongoing work, the line of research may point to new therapies and drug combinations for these metastases that represent the most dangerous aspects of prostate cancer.
-end-


University of Colorado Anschutz Medical Campus

Related Prostate Cancer Articles:

The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.
Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.
First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.
Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.
CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.
Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
Patient prostate tissue used to create unique model of prostate cancer biology
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
Moffitt Cancer Center awarded $3.2 million grant to study bone metastasis in prostate cancer
Moffitt researchers David Basanta, Ph.D., and Conor Lynch, Ph.D., have been awarded a U01 grant to investigate prostate cancer metastasis.
More Prostate Cancer News and Prostate Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.