Shining a Light on New Approaches for Ovarian Cancer Treatment and Detection

September 18, 2025 by

For many patients, the journey with ovarian cancer begins with uncertainty and a late-stage diagnosis, making treatment and recovery especially difficult. While most cases are diagnosed at advanced stages, resulting in low cure rates, recent advances are bringing renewed hope, particularly for patients battling rare forms like low-grade serous ovarian cancer (LGSOC). Progress in targeted therapies and clinical research is beginning to reshape outcomes and offer new possibilities for patients and their families. 

Take for example, Mary Katherine Riley, featured in the AACR Cancer Progress Report 2025, a 52-year-old special education teacher and mother of two who embodies this spirit of hope. Diagnosed with stage 3 LGSOC in 2019, Riley underwent surgery and six rounds of chemotherapy, initially experiencing no evidence of disease. However, LGSOC is known for its high recurrence rate, affecting over 80% of patients. When her ovarian cancer recurred in 2023, Riley’s doctor recommended a clinical trial for an investigational targeted therapy: avutometinib in combination with defactinib. This pivotal decision, driven by trust and a desire to contribute to research, led to a complete response for Riley. Today, Riley continues to take the now FDA-approved combination of avutometinib and defactinib (Avmapki Fakzynja Co-pack). She strongly advocates for funding cancer research, stating, “I’m living proof, basically, that a trial study and the research helped save my life” and will benefit others with her type of cancer.  

How This New Targeted Treatment for Ovarian Cancer Works 

Avutometinib is designed to stop certain signals (MEK1/2 kinase activities) that tell cancer cells to grow. It essentially “clamps” or “glues” two proteins together (RAF and MEK) to keep them inactive, blocking abnormal signals that promote cancer growth.  

Defactinib is a FAK inhibitor. FAK is another protein involved in the invasion and metastasis of tumor cells by regulating the activation of the RAS/RAF/MEK/ERK signaling pathway. This drug blocks it, further disrupting the cancer’s ability to thrive. 

Together, these therapies work to blunt the cancer-promoting impact of abnormal KRAS activity by blocking specific signaling pathways associated with malignant growth. Lab studies highlighted during the AACR Annual Meeting 2025 showed the combination of avutometinib and defactinib caused tumor regressions in five out of six animals, while each drug alone only slowed tumor growth without causing regression. This combination also appears to overcome ways that cancer cells might try to resist treatment, including pathways like MYC and PI3K signaling. 

In a phase II study called RAMP-201, the combination showed a higher overall response rate (ORR): 31% in the overall LGSOC patient population and a 44% ORR in patients with a KRAS mutation. This means 44% of the patients with KRAS-mutated LGSOC saw their tumors shrink or disappear, and these responses lasted from 3.3 months to 31.1 months.  

Understanding the Different Types of Ovarian Cancer 

Ovarian cancer encompasses a diverse group of malignancies. They are generally classified into epithelial, germ cell, and stromal cancers. Of the epithelial ovarian cancers, LGSOC, the subtype Riley faced, is rare, accounting for approximately 10% of all serous ovarian carcinomas. Patients with LGSOC are typically diagnosed at a younger age and, while often experiencing longer overall survival compared to those with high-grade serous ovarian carcinoma (HGSOC), their tumors demonstrate lower response rates to conventional platinum-based chemotherapy. This distinct biology is frequently characterized by aberrations in MAPK pathway-associated genes, with common KRAS, BRAF, or ERBB2 mutations.  

In contrast to LGSOC, HGSOC is the most common and aggressive subtype of epithelial ovarian cancer, accounting for approximately 70% of cases. HGSOC typically presents at an advanced stage and is characterized by widespread genomic instability, frequent TP53 mutations, and a high degree of intratumoral heterogeneity, which means the existence of distinct tumor cell populations (with different molecular and phenotypical profiles) within the same tumor specimen. 

The Ongoing Challenge of Ovarian Cancer Early Detection 

Despite new treatment advances in ovarian cancer, one of the major hurdles is early detection. Currently, 70%-75% of ovarian cancer cases are diagnosed at advanced stages (3 or 4), where the five-year survival rate around 30%. There is no universally accepted method for ovarian cancer screening. CA125 is a protein found in the blood that can be made by cells in the ovaries and other parts of the body. Higher levels of CA125 are often seen in ovarian cancer. It is currently used as one of the serological tests in cases when an ovarian neoplasm is suspected, but it lacks adequate specificity or sensitivity for effective screening.  

Blood tests to measure markers like CA125, HE4, and CA72.4 can be used to screen for ovarian cancer. 

The past decade, however, has seen adaptations of CA125 screening alongside transvaginal sonography (TVS), which  is a procedure used to examine the vagina, uterus, fallopian tubes, ovaries, and bladder through the use of sound waves. The Risk of Ovarian Cancer Algorithm (ROCA), for example, is a combination of protocols and calculations that analyzes trends in annual CA125 values over time, prompting imaging only for a small fraction of patients with rising levels. The NROSS trial demonstrated that a two-stage strategy using CA125 followed by TVS achieved a positive predictive value of 50% for detecting ovarian cancers and a 70% detection rate for early-stage (1-2) cancers, significantly reducing late-stage (3-4) disease by 30%-34% compared to controls.  

The Horizon of Ovarian Cancer Early Detection 

Recent years have seen a rapid development of novel diagnostic methods to enhance sensitivity and detection lead time. This can help professionals catch disease at earlier stages, increasing the rate of survival. 

  • Protein biomarker assays: Measuring protein levels like the Human Epididymis Protein 4 (HE4) and CA72.4 in the blood alongside CA125 screening may be highly effective, especially in cases where CA125 measurements alone may fall short, according to a study published in Cancer Discovery. By leveraging a machine learning model, the study found that combining HE4 data with CA125 increased the detection sensitivity of stage 1 ovarian cancers to 72%, an improvement compared to the 34% sensitivity achieved using CA125 alone. 
  • Lipidomics profiling: A study published in Cancer Research Communications showed that lipidomic and proteomics profiling, which is the study of tiny fat molecules and proteins in cancers as they progress, could be used alongside modern machine learning methods. The study presents a machine learning model that could distinguish early-stage ovarian cancer from other gynecologic and gastrointestinal conditions with 88% accuracy.  
  • MicroRNAs (miRNAs): These are small molecules that are responsible for gene expression. miRNAs circulate in body fluids, and changes in their profiles are being investigated as potential early ovarian cancer biomarkers. Researchers who presented work at the AACR Annual Meeting 2025 showed that the levels of a specific miRNA (miR-203a) determined by blood tests were especially high in aggressive ovarian cancers and could even make tumors more resistant to chemotherapy. This discovery points to miR-203a as both a potential early warning sign and a new target for future treatments. 
  • Advanced imaging techniques: Advances in imaging tools are increasingly being tested for precise identification of carcinomas, making early detection more accurate. A study presented at the AACR Annual Meeting 2025 showcased “OVASEEK,” a special imaging system that found early disease changes in fallopian tubes that standard tests missed in about one out of five samples. 

Studying Recurrence and Drug Resistance 

Another significant barrier to treating advanced-stage ovarian cancer is recurrence. Like the field of early detection, however, this area of research has also expanded greatly. Researchers are testing better techniques to measure relapse indicators like minimal residual disease and new combinations of existing methods to identify multidrug resistant phenotypes for epithelial ovarian cancer. 

  • Circulating tumor DNA (ctDNA) assays: Often referred to as “liquid biopsy,” this noninvasive method analyzes tumor-specific mutations in cell-free DNA from blood. ctDNA positivity after initial therapy has been linked to worse progression-free survival and overall survival in patients with advanced stage HGSOC, according to research published in Clinical Cancer Research. The study found that approximately half of patients in clinical remission still harbor surgical MRD, which is an independent negative prognostic factor for overall survival.  
  • Cutting-edge spatial transcriptomic and proteomic assays: Spatial transcriptomics technologies detect gene expression levels in cells within intact tissue, while preserving the spatial location of each cell. One of the limitations of this technique is the computational complexity of the data produced. Advances in technology and the creation of sophisticated statistical models like the one in a study presented at the AACR Annual Meeting 2025 can overcome this. The researchers revealed significant multidrug resistance properties of several persistent phenotypes in over 320 epithelial ovarian cancer patients and unveiled sensitivity of others to alternate FDA-approved drug classes. This means that existing drugs can be used more effectively by matching them with the specific cell populations that are identified in this study. 

A Call for Continued Support 

Riley’s journey, from recurrence to remission with a new groundbreaking treatment for ovarian cancer, is living proof of what science, clinical trials, and unwavering hope can achieve. For patients facing rare cancers like LGSOC, where conventional therapies often fall short, research-driven breakthroughs are lifelines. Every clinical trial, research grant, and act of advocacy brings us closer to a future where earlier detection, precision therapies, and lasting cures are within reach.  

Hope is not passive, it is action. By supporting research, raising awareness, and standing with patients and survivors, we help transform hope into reality. Together, we can build a future where fewer women face ovarian cancer, and more stories end like Riley’s does, with renewed life, resilience, and possibility. 

For more about the latest advances in understanding and treating ovarian cancer, keep an eye out for Cancer Research Catalyst’s coverage of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research.