Study of the Week: CRISPR-Cas9 Genome Editing for Cancer Treatment

Welcome to study of the week, a new series from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.


This week’s study is…

CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy

We previously published a story about this research in a story titled “CRISPR-Cas9’s Gene Editing Potential in Cancer Therapy,” which can be found here. The study was originally published in the research journal Science Advances. You can view the full text of it here.

What Happened?

CRISPR-Cas9 genome editing has been widely hailed as a breakthrough development in medicine that has the potential to have major impacts in a wide variety of diseases, including cancer. However, there hasn’t been much development in using CRISPR to treat cancer. This is primarily because of possibility of toxicity using established delivery methods and the inefficiency of gene editing in tumor cells. This study describes a new method of delivery using lipid nanoparticles that resolves these issues.

The scientists selected cells from glioblastoma (line GBM 005), an almost universally lethal brain cancer, and ovarian cancer, specifically disseminated ovarian adenocarcinoma (line OV8). Both cell lines selected were considered difficult to treat, aggressive, and incurable. Lipid nanoparticles (LNPs) are an approved nonviral delivery system, but this was the first study to explore its use in cancer treatment. 

The genome editing acted on the PLK1 gene, which codes for a kinase that plays a vital role in mitosis, a process of cell division. Using the CRISPR-lipid nanoparticle (cLNP) delivery system, 84 percent genomic editing was achieved in GBM 005 and 91 percent genomic editing was achieved in OV8. In summary, the cLNPs were able to successfully disrupt the activity of the targeted gene, halt the cell division cycle, and kill the cancer cells. 

This method also appeared to be relatively safe following systemic administration in mouse models, and there were no indicators of toxicity at therapeutically meaningful doses. In addition, a single administration of the PLK1-cLNPs was sufficient to improve survival and inhibit tumor growth in GBM 005. Tumor growth was inhibited by 50 percent and survival improve by 30 percent. PLK1-cLNPs which targeted the epidermal growth factor receptor (EGFR) was also effective in treating disseminated ovarian adenocarcinoma. Survival in this mouse model increased by 80 percent.   

About Glioblastoma

Glioblastoma is a rare brain cancer. It is also the most aggressive cancer to originate in the brain. It is characterized by its rapid progression and poor response to most treatments. In most cases, the cause of glioblastoma is not known. A small number of cases evolve from another type of tumor called an astrocytoma. Risk factors for glioblastoma include genetic disorders such as Turcot syndrome and neurofibromatosis, exposure to pesticides, smoking, and a career in petroleum refining or rubber manufacture. Symptoms of glioblastoma include personality changes, headaches, memory loss, seizures, vomiting, and nausea; patients may lose consciousness in late stages. Treatment approaches include anticonvulsants, steroids, chemotherapy, radiation, and surgery. While a small number of patients can survive for several years, treatment is often ineffective, with the tumor relapsing quickly. Five year survival rate is only three percent. To learn more about glioblastoma, click here.

About Ovarian Cancer

Ovarian cancer can appear on or within the ovary. Ovarian cancer rarely causes distinctive symptoms in its early stages, so many patients are often diagnosed with advanced disease. The risk of getting ovarian cancer is connected to how long a female has ovulated during her life; females who ovulate for longer periods are at greater risk. Late menopause or early puberty are risk factors, as are not having children, fertility medication, certain genetic variants and mutations (such as BRCA mutations), and exposure to talc, herbicides, and pesticides. Some symptoms of ovarian cancer include fatigue, bloating, a feeling of fullness, loss of appetite, indigestion, abdominal swelling, and pelvic pain. Treatment can include chemo, radiation, surgery, hormone therapy, and immunotherapy. There are many different kinds of ovarian cancer. Five year survival rate is 45 percent in the US. To learn more about ovarian cancer, click here.

Why Does it Matter?

The evolution of cancer treatment has been a long and arduous process, but there have definitely been major improvements in recent years and decades. Some of the latest advances, such as immunotherapies and molecularly targeted inhibitors, have allow for major improvements in treatment response across many different cancer forms, all while reducing adverse effects and overall toxicity when compared to earlier approaches like chemotherapy.

However, there are still some cancers that can’t be treated very effectively. In many forms, recurrence or relapse is all too common and many cancers are able to adapt and develop treatment resistance. These continued deficiencies mean that development of new approaches, such as CRISPR, is just as urgent as ever. This study has demonstrated a potential method for this technology to be used effectively in cancer, and the fact that it was able to have impacts in notoriously difficulty forms such as glioblastoma is all the more encouraging.

A major advantage that CRISPR could hold over other treatments is that it can have therapeutic benefit in just one or a handful of doses. Many cancer therapies need to be administered repeatedly for maximum impact, and returns often diminish over time as resistance appears or toxicity increases. While there is still a long way to go before a CRISPR approach would be fully developed for cancers, this study is a substantial step forward.

Check back the Monday of each week for the next installment in this series.

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