Ovarian cancer: A nanodrug treatment approach shows promise

  • About 314,000 women around the world had ovarian cancer in 2020.
  • There is currently no cure for ovarian cancer.
  • Researchers from Tel Aviv University in Israel have unveiled a new potential treatment for ovarian cancer using RNA-based nanodrugs.
  • They reported an 80% survival rate in animal models.

Ovarian cancer is the eighth most common cancer in women worldwide, affecting almost 314,000 women globally in 2020.

There is currently no cure for ovarian cancer and doctors treat the condition with a combination of chemotherapy, surgery, immunotherapy, radiation therapy, and other targeted therapies.

Now researchers from Tel Aviv University in Israel have unveiled a new potential treatment for ovarian cancer using RNA-based nanodrugs. Researchers reported an 80% survival rate in animal models.

The study was recently published in the journal Science Advances.

What is ovarian cancer? 

Ovarian cancer occurs when cells near or inside the ovaries repeatedly develop mutations in their DNA. This causes them to grow and multiply much quicker than they normally should, ultimately creating a tumor.

There may not be any signs of ovarian cancer in its earliest stage. Some common symptoms of ovarian cancer include:

  • vaginal bleeding
  • pressure and/or pain in the lower abdomen or pelvis
  • bloating
  • pain in the back
  • urination and/or bowel changes
  • tiredness
  • loss of appetite
  • unexplained weight loss
  • nausea and/or indigestion.

Anyone can get ovarian cancer. However, there are some risk factors that can increase a person’s chance of developing the disease. These include:

  • family history of ovarian or breast cancer
  • personal history of breast cancer
  • age — most cases develop after menopause
  • having children later in life
  • never having had a pregnancy
  • undergoing hormone replacement therapy
  • obesity
  • smoking.

What are RNA-based nanodrugs? 

Nanoparticles are extremely small particles of matter measuring between 1 and 100 nanometers in diameter. In medical applications, nanoparticles are used as microscopic transporters for administering drug and gene therapies.

These nanoparticles can also be used to deliver RNA therapy. This was previously seen in the mRNA-based COVID-19 vaccines that used a nanocarrier called lipid nanoparticles.

Additionally, previous studies have examined the use of RNA-based nanomedicine for other cancers, including lung cancer, lymphoma, colorectal cancer, and renal cancer.

Using nanodrugs to treat ovarian cancer

According to Dr. Sushmita Chatterjee, a postdoctoral fellow in the lab of Prof. Dan Peer at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University and lead author of this study, nanodrugs, such as lipid nanoparticles, have the ability to encapsulate short or long sequences of ribonucleic acids (RNA).

“RNAs can perform various functions; [for instance,] short RNA can silence gene expression,” she told Medical News Today. “These sequence-specific RNA can cleave mRNA and are called siRNA.”

Dr. Chatterjee said an RNAi-based screening study showed that the protein CKAP5 (cytoskeleton-associated protein) is the therapeutic target with the most potential in the treatment of multiple myeloma, indicating the significance of this protein.

“Since CKAP5 plays [an] important role during mitosis [a process of cellular division], we hypothesized that therapeutic silencing of [the] CKAP5 [gene that encodes this protein] might show selective vulnerability in cancer cells with high genomic instability,” she continued.

“To execute our study, we used siRNA-lipid nanoparticle mediated silencing of CKAP5 as siRNA is highly specific and efficient for silencing gene targets, and at present lipid nanoparticles are at the forefront of RNA delivery.”

Dr. Chatterjee added that using siRNA against CKAP5, which included encapsulating them in lipid nanoparticles, helps provide a slow release of the payload of siRNA, better penetration into the tumor cells, and shows the least toxic effects.

How a nanodrug can silence CKAP5

For this study, Dr. Chatterjee and her team identified a genetically unstable mutation resistant to both chemotherapy and immunotherapy in the tissues of ovarian cancer. Using an animal model, they targeted these cells with the RNA-based nanodrug designed to silence CKAP5.

At the conclusion of the study, scientists reported an 80% survival rate in animal models.

Dr. Chatterjee said they were surprised to see an 80% survival rate for four main reasons.

“First, inhibiting the growth of cancer cells is highly challenging as cancer cells develop various mechanisms to combat the effects of drugs,” she detailed. “Secondly, siRNA leads to transient silencing of the target gene and the tumors may recur once the siRNA-mediated effects are over.”

“Third, our model was a chemoresistant ovarian cancer tumor which is [a] highly aggressive form of cancer,” Dr. Chatterjee continued. “And fourth, most of the genes have redundant functions, meaning [that], in [the] absence of a gene, its function can be executed by another gene.

“Due to all these reasons, it’s very hard to achieve significant inhibition of tumor growth by silencing only one gene. Therefore [the] observation of 80% survival was actually a eureka moment for us.”
– Dr. Sushmita Chatterjee

The next steps in this research

Reflecting on the next steps in this research, Dr. Chatterjee said they are “highly optimistic and positive” about their results regarding CKAP5.

“However it will be important to identify the patient group where CKAP5 silencing may lead to better therapeutic effects,” she noted. “For example, we have shown in our study that CKAP5 silencing leads to selective vulnerability in cancer cells with high genomic instability. It will be important to establish it further in clinical settings.”

Dr. Chatterjee said she and her team would like to investigate the therapeutic benefit of CKAP5 silencing in combination with targeted molecular therapies.

“Since the majority of ovarian cancer patients are diagnosed at late stages, it will be also interesting to investigate the therapeutic effects of CKAP5 silencing in a metastasized/ late-stage cancer model,” she added. “It can be also advantageous to develop a CRISPR-based system for CKAP5 silencing therapy.”

Why we need new therapies

After reviewing this study, Dr. Hyo Park, a gynecologic oncologist at the Women’s Health and Wellness Institute at Saint John’s Cancer Institute, who was not involved in the study, told MNT she is always excited to see new therapeutic developments in the treatment of ovarian cancer.

“[The] majority of ovarian cancer cells will eventually develop resistance to chemotherapy and only half of ovarian cancer patients are candidates for newer targeted therapy options such as PARP inhibitors,” she explained.

“Unfortunately, immunotherapy drugs have not had as much success so far in treating ovarian cancer compared to other solid tumors or liquid tumors,” she added.

Overcoming challenges

“What makes developing novel therapeutic drugs for ovarian cancer challenging is that ovarian cancer is relatively genetically stable and does not carry many targetable mutations,” Dr. Park continued.

“This study is especially intriguing because the researchers have identified a new potential treatment target — CKAP5 — and demonstrated a promising novel approach — LNP-mediated delivery of gene-silencing siRNA — to silence this target and cause cancer cell death,” she added.

MNT also spoke with Dr. Krishnansu Tewari, a gynecologic oncologist at MemorialCare Todd Cancer Institute Women’s Specialty Center at Long Beach Medical Center in Long Beach, CA, who was not involved in the study, about this research. Dr. Tewari was more inclined to caution.

“My first reaction to this study is that this is a laboratory study and there’s a long way to go before we can consider this as a viable and effective treatment for ovarian cancer,” he said. “Because the technique silences microtubule-associated genes it may be potentially useful for any cancers during DNA replication.”

“[The] next step is to further develop the methodology to deliver silencing RNAs to patients and perhaps to clarify the cancers for which this may be potentially effective,” Dr. Tewari added. “The researchers selected ovarian cancer but did not have a molecular target specific for ovarian cancer.”

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