A promising nanodrug therapeutic approach

Ovarian cancer occurs when cells are near or inside the ovaries. ovary Repeat DNA mutations. This causes them to grow and multiply much faster than normal, eventually creating tumors.

In the early stages of ovarian cancer, there may be no symptoms. Common symptoms of ovarian cancer include:

Anyone can get ovarian cancer. However, there are some risk factors that increase the likelihood of developing the disease. These include:

According to Dr. Sushmita Chatterjee, a postdoctoral fellow in Professor Dan Peer’s lab at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University and lead author of the study, nanodrugs such as lipid nanoparticles have the ability to be encapsulated. I’m here. A short or long sequence of ribonucleic acid (RNA).

“RNA can perform a variety of functions. [for instance,] short RNA can be silenced gene expression‘ she said medical news today“These sequence-specific RNAs can cleave mRNAs, siRNA“

Dr. Chatterjee said: RNAi-based screening studies shown to be a protein. CKAP5 (cytoskeleton-associated proteins) are the most promising therapeutic targets in the treatment of multiple myeloma, demonstrating the importance of this protein.

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

“We used siRNA-lipid nanoparticle-mediated silencing to carry out our study CKAP5 Because siRNAs are highly specific and efficient in silencing gene targets, lipid nanoparticles are currently at the forefront of RNA delivery. “

Dr. Chatterjee CKAP5We show that encapsulating them in lipid nanoparticles helps provide sustained release of siRNA payloads, better penetration into tumor cells, and has the least toxic effects.

For this study, Dr. Chatterjee and her team identified genetically unstable mutations in ovarian cancer tissue that are resistant to both chemotherapy and immunotherapy. Using animal models, they targeted these cells with RNA-based nanodrugs designed to silence them. CKAP5.

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

Dr. Chatterjee said he was surprised by the 80% survival rate for four main reasons.

“First, it is very difficult to inhibit cancer cell growth because cancer cells develop different mechanisms to counter the effects of drugs,” she elaborated. “Second, siRNAs can cause transient silencing of target genes, and tumor recurrence can occur once the siRNA-mediated effects cease.”

“Third, our model was a chemoresistant ovarian cancer tumor. [a] It’s a very aggressive cancer,” Dr. Chatterjee continued. “And fourth, most genes have redundant functions. [that]of [the] If a gene is absent, its function may be performed by another gene.

“For all these reasons, it is very difficult to achieve significant suppression of tumor growth by silencing just one gene. [the] The observation of 80% survival was indeed a moment of discovery for us. “
– Dr. Sushmita Chatterjee

Reflecting on next steps in the study, Dr. Chatterjee said he was “very optimistic and positive” about the results for: CKAP5.

“But it is important to identify patient groups. CKAP5 Silencing may lead to better therapeutic effects,” she noted. CKAP5 Silencing leads to selective vulnerability of cancer cells with high genomic instability. Further establishment in the clinical setting is important. “

Dr. Chatterjee said she and her team CKAP5 Silencing in combination with targeted molecular therapy.

“It would also be interesting to investigate the effects of ovarian cancer treatment, as the majority of ovarian cancer patients are diagnosed at a later stage. CKAP5 silence in transferred/ terminal cancer model,” she added. “again, Crisperbase system for CKAP5 silencing therapy. “

After reviewing the study, Dr. Hyo Park, a gynecologic oncologist at the Institute for Women’s Health and Wellness at the St. John’s Cancer Institute, who was not involved in the study, said: MNT She is always looking forward to new treatments being developed in the treatment of ovarian cancer.

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

“Unfortunately, immunotherapeutic drugs have so far been less successful than other drugs in treating ovarian cancer. solid tumor again liquid tumor,” she added.

“What makes the development of new treatments for ovarian cancer difficult is that ovarian cancer is relatively genetically stable and does not have many targetable mutations,” continued Dr. Park. rice field.

“This study is of particular interest because the researchers identified a new potential therapeutic target. CKAP5 — and demonstrated a promising new approach — LNP-mediated delivery of gene-silencing siRNAs — to silence this target and cause cancer cell death,” she added.

MNT We also spoke with Dr. Krishnanth Tewari, a gynecologic oncologist at the Women’s Specialty Center at Memorial Care Todd Cancer Institute at Long Beach Medical Center in Long Beach, California, about the study. tended to be careful.

“My initial reaction to this study is that this is a laboratory study and there is still a long way to go to consider this a viable and effective treatment for ovarian cancer.” It silences microtubule-associated genes, so it may be useful in any cancer during DNA replication.”

“[The] The next step is to further develop methodologies for delivering silencing RNA to patients and possibly identify cancers where this may be effective,” added Dr. Tewari. “The researchers chose ovarian cancer, but they didn’t have a specific molecular target for ovarian cancer.”