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Study Identifies Two Proteins as Markers of Response to Neoadjuvant Chemotherapy for Ovarian Cancer

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Key Points

  • A study of women with ovarian cancer has found that patients who relapse shortly after neoadjuvant chemotherapy to shrink their tumor prior to surgery have high levels of expression of HGF and c-Met proteins.
  • The levels of HGF and c-Met expression in patients with ovarian cancer could help determine clinical criteria of eligibility for neoadjuvant chemotherapy and prevent patients with these proteins from undergoing unnecessary treatment.
  • Inhibitors of the HGF and c-Met pathway may improve the efficacy of neoadjuvant chemotherapy prior to surgery.

A study by researchers from Danbury Hospital Biomedical Research Institute in Connecticut has found that patients with ovarian cancer who relapse shortly after neoadjuvant chemotherapy to shrink their tumor prior to surgery have high levels of expression of HGF and c-Met proteins. The researchers’ discovery may help identify which patients may not benefit from neoadjuvant therapy and prevent patients with these proteins from undergoing unnecessary treatment. The study by Mariani et al is published in Oncotarget.

Study Method and Findings

An integrated approach was used to investigate the biology of the ovarian cancer tumor’s response to chemotherapy, including gene/microRNA expression coupled with quantitative fluorescent immunohistochemistry. Analysis started with a panel of prognostic microRNAs. Expression of a panel of microRNAs was screened in a discovery set of 85 patients with ovarian cancer. An analysis of the potential targets was conducted in the same RNAs. The researchers discovered several prevalent microRNAs, especially microRNA miR-193a-5p and found that two genes, HGF and MET, were significantly correlated with microRNA miR-193a-5p.

Analysis of protein expression in tumor samples taken before and after neoadjuvant chemotherapy demonstrated that both HGF and c-Met are increased after neoadjuvant chemotherapy. In addition, patients who relapsed shortly after neoadjuvant treatment exhibited the highest relative basal expression of both HGF and c-Met. Conversely, patients with low relative expression of HGF and c-Met tended to have longer platinum-free interval (PFI) and a better outcome.

“People believe when you have high expression of a gene that you should have a high expression of the protein, but this is not always the case,” said Cristiano Ferlini, MD, PhD, Director of Biomedical Research at Danbury Hospital Biomedical Research Institute. “That is one of the important findings of our paper, because we believe if you are going to use a drug, you have to target the problem and not the gene because, like in this case, you can have low expression of the gene and high expression of the protein.”

Next Steps

According to Dr. Ferlini, a prospective clinical study to validate his retrospective analysis of patients with ovarian cancer is being planned and should be underway in 6 to 9 months.

“This finding potentially creates an opportunity to improve diagnostic and therapeutic strategies for a clinical category of ovarian cancer patients who minimally benefit from chemotherapy and debulking surgery,” concluded the study authors.

According to the National Cancer Institute, ovarian cancer is the fifth leading cause of cancer death among women in the United States and has the highest mortality rate of all gynecologic cancers. It is estimated that 21,980 new cases of ovarian cancer will be diagnosed this year, and 14,270 women will die of this disease.

The researchers declared no conflicts of interest. 

Funding for this study was provided by Associazione Italiana Ricerca sul Cancro, Associazione OPPO e le sue stanze ONLUS, the Ruth C. Donovan Cancer Research Program, and Mr. and Mrs. Ruggles.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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