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Gamechanging treatment cures lethal form of cancer, study finds

[Sept. 19, 2023: Staff Writer, The Brighter Side of News]


Researchers at Gladstone Institutes and UC San Francisco—including Theodore Roth (left) and Franziska Blaeschke (center)—used a new method to screen 10,000 combinations of gene edits in immune cells engineered to fight cancer. (CREDIT: Gladstone Institutes)


In a major step forward against one of the deadliest forms of cancer, researchers have unveiled a promising treatment with the potential to revolutionize the way epithelial ovarian cancer is combatted. Epithelial ovarian cancer, often regarded as the most lethal subtype of ovarian cancer, might have met its match in a new therapy based on the 225Ac-DOTA system.


Epithelial ovarian cancer often metastasizes as peritoneal carcinomatosis, where the malignant cells pervade the peritoneal cavity, drastically limiting treatment options and survival outcomes. Alarmingly, the five-year survival rates for individuals diagnosed with this advanced-stage disease stand between 18 to 46 percent. Many succumb to the disease due to the overwhelming peritoneal disease burden and consequent malignant bowel obstructions.


 
 

The newly introduced pre-targeted radioimmunotherapy (PRIT) system, specifically targeting the HER2 protein—a marker frequently expressed in ovarian cancer—offers a beacon of hope. The therapy, dubbed as "anti-HER2 225Ac-PRIT", has shown remarkable results in a preclinical setting, significantly reducing the effects of an otherwise fatal disease.


The revelation about this innovative therapy was published in the esteemed Journal of Nuclear Medicine.


 

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"Due to the explosion of immune and targeted therapies in the past few decades—particularly those targeting HER2—there is increasing interest in the potential role of alternative, more innovative therapies to cure epithelial ovarian cancer,” said Sarah M. Cheal, PhD, an expert from the Molecular Imaging Innovations Institute at Weill Cornell Medical College in New York.


She further elaborated, “In this study, we adapted our PRIT system to target HER2 in epithelial ovarian cancer and explored whether this could effectively treat the disease without significant toxicity.”


 
 

To understand the effectiveness of this novel treatment, a preclinical study was conducted with five groups of eight to ten nude mice, each laden with peritoneal carcinomatosis tumors. Two of these groups were administered one or two cycles of anti-HER2 225Ac-PRIT. Simultaneously, the rest received alternative treatments or none at all, acting as control groups. Over a span of 154 days, meticulous records of the mice's weekly weights and tumor progression were kept.


Abstract: Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. (CREDIT: Journal of Nuclear Medicine)


The prognosis for untreated mice was grim, with tumors metastasizing quickly, leading to a median survival duration of roughly four months. In stark contrast, those treated with anti-HER2 225Ac-PRIT displayed exemplary results. After the 154-day study period, a staggering 75 percent of the treated mice were clinically cured. Moreover, these treatments were well-tolerated, paving the way for further human trials.


 
 

Steven M. Larson, MD, from the Department of Radiology at Memorial Sloan Kettering Cancer Center in New York, provided valuable insight into the study’s significance. "In this study, we achieved high potency with anti-HER2 225Ac-PRIT while maintaining an acceptable safety profile. These findings suggest that when scaled to human patients, we can achieve curative tumor radiation-absorbed doses without major normal organ toxicity."


Minimal to mild radiation nephropathy was observed in mice treated with 1 (37 kBq) or 2 (74 kBq) cycles of HER2 225Ac-PRIT. (CREDIT: Journal of Nuclear Medicine)


Taking the discussion further, Nai-Kong V. Cheung, MD, PhD, from the Department of Pediatrics at Memorial Sloan Kettering Cancer Center in New York, pointed out the adaptability of the treatment. "Since DOTA-based PRIT is modular, it can be adapted to other cancers. Next-generation PRIT using SADA (Self-Assembling DisAssembling Antibody) has the potential for broad applications for compartmental (e.g., peritoneal) as well as systemic theranostics in oncology."


 
 

This gamechanging study serves as a testament to the possibilities that await in the realm of oncology. While preliminary, these findings offer renewed hope for countless individuals affected by this lethal variant of ovarian cancer.


Chart depicting the 4 stages of ovarian cancer. (CREDIT: Weill Cornell Medical College)


Types of ovarian cancer


According to the Mayo Clinic, the type of cell where the cancer begins determines the type of ovarian cancer you have and helps your doctor determine which treatments are best for you. Ovarian cancer types include:

  • Epithelial ovarian cancer. This type is the most common. It includes several subtypes, including serous carcinoma and mucinous carcinoma.

  • Stromal tumors. These rare tumors are usually diagnosed at an earlier stage than other ovarian cancers.

  • Germ cell tumors. These rare ovarian cancers tend to occur at a younger age.


 
 

Risk factors


Factors that can increase your risk of ovarian cancer include:


Older age. The risk of ovarian cancer increases as you age. It's most often diagnosed in older adults.


Inherited gene changes. A small percentage of ovarian cancers are caused by genes changes you inherit from your parents. The genes that increase the risk of ovarian cancer include BRCA1 and BRCA2. These genes also increase the risk of breast cancer.


Several other gene changes are known to increase the risk of ovarian cancer, including gene changes associated with Lynch syndrome and the genes BRIP1, RAD51C and RAD51D.


Family history of ovarian cancer. If you have blood relatives who have been diagnosed with ovarian cancer, you may have an increased risk of the disease.

Being overweight or obese. Being overweight or obese increases the risk of ovarian cancer.


Postmenopausal hormone replacement therapy. Taking hormone replacement therapy to control menopause signs and symptoms may increase the risk of ovarian cancer.


Endometriosis. Endometriosis is an often painful disorder in which tissue similar to the tissue that lines the inside of your uterus grows outside your uterus.


 
 

Age when menstruation started and ended. Beginning menstruation at an early age or starting menopause at a later age, or both, may increase the risk of ovarian cancer.


Never having been pregnant. If you've never been pregnant, you may have an increased risk of ovarian cancer.






For more science news stories check out our New Innovations section at The Brighter Side of News.


 

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.


 
 

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