New therapy could reverse drug resistance

For this study, Prof. Johann De Bono, and his team targeted myeloid white blood cells, which normally help defend the body against infections. However, these types of blood cells are also usually pulled into a tumor, helping it grow and resist treatment.

“Myeloid cells are part of the immune system. In normal conditions, they are rapidly recruited to sites of inflammation in the body, where they help to mount a defense against any invading pathogens,” Prof. De Bono, professor in experimental cancer medicine at The Institute of Cancer Research, London, consultant medical oncologist at The Royal Marsden NHS Foundation Trust, and one of the authors of this study told Medical News Today.

“In cancer, it’s a different story. Myeloid cells are also pulled into tumors. When tumor cells are stressed, they can enter a non-proliferating state called ‘senescence’ and become ‘cytokine factories,’ manufacturing proteins which attract myeloid cells into tumors where they support tumor growth, division, and survival. They can also send further signals to the bone marrow to recruit more ‘conspirator’ myeloid cells to enter the tumor and the cycle continues,” he explained.

During the study, scientists used a combination of an experimental drug called AZD5069 and a hormone therapy commonly used to treat prostate cancer called enzalutamide to stop myeloid cells from being pulled into tumors.

“This drug works by blocking myeloid cells being attracted into the tumor. If these cells cannot get into the tumor, they cannot carry out their usual tumor-promoting activities,” Prof. De Bono said.

Of the 21 study participants with metastatic castration-resistant prostate cancer, researchers reported five of them responded to the treatment by either their tumor shrinking in size by over 30%, a decrease in circulating levels of prostate-specific antigen (PSA), or a drop in circulating tumor cell blood levels.

The scientists stated that participants who received the treatment also experienced a drop in myeloid cells, and biopsies after treatment also revealed fewer myeloid cells within their tumors.

“It was tremendously exciting to see five study participants show a response to the treatment. It proves for the first time that targeting myeloid cells rather than the cancer cells themselves can benefit patients. Developing new drugs can take many years, but we plan to further work on this in clinical trials, develop better drugs, and hopefully take this forward as a treatment strategy.”
— Prof. Johann De Bono

And might this process of targeting myeloid white blood cells be used to treat other types of cancer?

“We know myeloid cells have a role in the promotion of other types of cancer, so we think the impact of this research could be broad, across multiple cancer types,” Prof. De Bono said.

Prostate cancer is a type of cancer that occurs in the prostate. The prostate is an organ that is part of the male reproductive system.

There are screening tests available for prostate cancer. At the earliest stage of prostate cancer, there may be no symptoms. If symptoms do occur, they usually include:

• trouble urinating or painful urination
• frequent urination
• blood in the urine or semen
• pain in the pelvis, hips, or back

Since prostate cancer requires testosterone to grow, treatments suppress this male sex hormone.

Castration-resistant prostate cancer occurs when a tumor continues to grow even though testosterone production has been slowed.

Metastatic castration-resistant prostate cancer is when the cancer spreads to other areas of the body, such as lymph nodes, bones, or other organs.

There is currently no cure for castration-resistant prostate cancer. Treatment for metastatic castration-resistant prostate cancer may include radiation therapy, hormone therapy, chemotherapy, and immunotherapy.

Over the past few years, researchers have been working on finding new therapies for castration-resistant prostate cancer.

“Cancer has a unique ability to evolve and become resistant to treatment, meaning the drugs we use to keep cancer under control will eventually stop working,” said Prof. De Bono.

“Treatments which open up new lines of attack against prostate cancer will be key to overcoming treatment resistance and extending men’s lives.”
— Prof. Johann De Bono

After reviewing this study, Dr. Mina M. Fam, medical director of urologic oncology at Hackensack Meridian Jersey Shore University Medical Center & Robotic Surgery at Ocean University Medical Center, told Medical News Today that this is an extremely exciting study using an innovative approach to manage a very challenging disease such as metastatic castration-resistant prostate cancer.

“This research could be a ‘game-changer’ not only for prostate cancer treatment but for several cancers, particularly aggressive and advanced cancers,” he added.

Dr. Fam explained that while localized prostate cancer has many effective treatments that can keep the cancer under control, patients with metastatic castration-resistant prostate cancer fail treatment with traditional androgen deprivation.

“Although there have been several advances in the treatment of metastatic castrate-resistant prostate cancer in recent years, even these treatments can fail over time,” he continued.

“[Metastatic castration-resistant prostate cancer] patients can progress with significant bone spread, urinary obstruction, and other painful complications that eventually lead to death from their prostate cancer. For that reason, it is exceedingly important to develop novel therapies for metastatic castrate-resistant prostate cancer to provide better survival and improved quality of life for these patients.”
— Dr. Mina Fam

MNT also spoke with Dr. Wael Harb, a board certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Fountain Valley, California about this research.

He commented that this is a very interesting and potentially promising approach.

“Traditionally, we always focus on the tumor cells itself, but more recently our understanding of what we call the tumor microenvironment,” Dr. Harb explained. “That means the cells and the environment around the cancer cells that might play a big factor in how the cancer progresses. So targeting the tumor microenvironment, rather than the cancer cells themselves, is an innovative strategy that warrants further exploration.”

Although this research is very promising, Dr. Harb pointed out it is an early clinical trial, and larger randomized trials are needed where scientists compare this approach to other treatment options, such as chemotherapy, to see what the results are.

“Can we keep the cancer under control for longer? Can we make the patient live longer? So if we are able to show based on randomized trials that this approach is better as far as giving longer time for patients and especially if it’s quality time, then this will become the new standard of care,” he said.