Navigation Links
Mechanisms of acquired chemoresistance in ovarian cancer identified
Date:8/14/2012

PHILADELPHIA The presence of multiple ovarian cancer genomes in an individual patient and the absence or downregulation of the gene LRP1B are associated with the development of chemoresistance in women with the high-grade serous cancer subtype of ovarian cancer whose disease recurs after primary treatment. These study results are published in Cancer Research, a journal of the American Association for Cancer Research.

David Bowtell, Ph.D., head of the Cancer Genomics and Genetic Program at the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues generated these data in one of the first studies to investigate using patient tumor samples as the mechanisms responsible for the emergence of chemotherapy resistance in high-grade serous ovarian cancer.

"High-grade serous cancers account for about two-thirds of deaths from epithelial invasive ovarian cancer," Bowtell said. "We were interested in identifying the molecular changes that occurred in a tumor between the time when a woman first presented for surgery and chemotherapy, and the time when the tumor recurred and eventually became resistant to chemotherapy."

To examine this, the researchers analyzed metastatic lesions from individual patients and 22 paired pretreatment and post-treatment tumor samples for spatial and temporal genomic variation.

"Spatial variation is a measure of genomic heterogeneity in different deposits of tumor present at primary surgery variation that the tumor could draw on to evolve over time, especially in the face of chemotherapy," Bowtell explained. "Temporal variation gives us an indication of how much the tumor changes over time, and after one or more lines of chemotherapy."

The researchers compared the level of genomic change among women who were initially chemosensitive and those who were resistant to primary chemotherapy. Tumors that were initially sensitive to chemotherapy but later became resistant evolved further than those tumors that were resistant from the outset. "We were surprised by the extent of variation that was present among the tumor deposits collected at surgery, and by how far the tumors could evolve during therapy," Bowtell said. "The existence of multiple cancer genomes in an individual patient could provide many opportunities for the cancer to circumvent chemotherapy and may help explain why it has been so difficult to make progress with this disease," he said.

The most frequently occurring genomic change found was a deletion and/or downregulation of LRP1B, which encodes a member of a family of proteins that transport lipids into cells. To validate their findings further, the researchers examined the effect of engineering gain or loss of LRP1B in ovarian cancer cell lines. Loss of LRP1B contributed to the emergence of resistance to liposomal doxorubicin, a type of chemotherapy, in women exposed to the drug during their treatment.

"Many women with high-grade serous ovarian cancer experience an excellent response to initial chemotherapy, but unfortunately the disease often returns and becomes resistant to treatment. Currently, we have few tools to predict response to chemotherapy in the relapse setting. LRP1B adds to a handful of other mechanisms so far identified," Bowtell said. "If we can comprehensively map the mechanisms that confer resistance, we may be able to predict whether some women are likely to respond to a certain drug or not, and find ways of reversing resistance."

The study forms part of the International Cancer Genome Consortium (ICGC). Bowtell said that international collaboration is needed to systematically map the emergence of chemotherapy resistance in ovarian cancer and other solid cancers, given that it is difficult to obtain paired pre- and post-treatment samples. He believes that the collection of biopsy tissue in the relapse setting will increasingly be seen as essential for predicting response in the clinic and understanding why treatment failure occurs.


'/>"/>
Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Researchers unfold the mechanisms underlying blood disorders
2. Aggregating instead of stabilizing: New insights into the mechanisms of heart disease
3. UCLA study to determine if copper surfaces can reduce hospital-acquired infections
4. Community-acquired MRSA cases on the rise in New York City, study suggests
5. Benefit of PET and PET/CT in ovarian cancer is not proven
6. Ovarian Transplants May Preserve Fertility in Young Cancer Survivors
7. Fertility preservation with cryopreservation of ovarian tissue: from experimental to mainstream
8. The prevention of hereditary breast and ovarian cancer by PGD is feasible
9. Internationally known expert in ovarian cancer to be honored at the ASCO Annual Meeting
10. UC Irvine study finds racial, economic disparities in ovarian cancer care, survival
11. U.S. Panel Rejects Ovarian Cancer Screening
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that covers care ... have a waiver for care if the client has a cognitive impairment diagnosis. ... for care, is often waived, so the benefits from their insurance start immediately,” said ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Ellevate Network, the ... business to advocate for action towards gender equality at their inaugural Summit in New ... the globe, and reached a social audience of over 3 million. To watch the ...
(Date:10/13/2017)... ... ... Yisrayl Hawkins, Pastor and Overseer at The House of Yahweh, has released a ... books in the Holy Scriptures, Revelation. The Book of Revelation paints a picture of ... have tossed it off as mere rubbish, but Yisrayl Hawkins says that is because ...
(Date:10/13/2017)... ... October 13, 2017 , ... Coveros, a leader in ... awarded a contract by the Center for Medicare and Medicaid Services (CMS). The ... enterprise use of Agile methodologies in a consistent and high value manner across ...
(Date:10/13/2017)... ... 2017 , ... “America On The Brink”: the Christian history of the United ... the creation of published author, William Nowers. Captain Nowers and his wife, Millie, ... spent thirty years in the Navy. Following his career as a naval aviator ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... , Oct. 10, 2017   West Pharmaceutical ... innovative solutions for injectable drug administration, today shared the ... ID Adapter for improving the intradermal administration of polio ... Skin Vaccination Summit in May 2017 by Dr. ... Polio Department, World Health Organization (WHO), and recently published ...
(Date:10/4/2017)... Centers for Disease Control and Prevention (CDC), influenza vaccination should take ... communities across Massachusetts , Connecticut , ... through the end of the month. *Some exclusions apply ... ... by the end of October, according to the Centers for Disease Control ...
(Date:10/2/2017)...  AllianceRx Walgreens Prime, the combined central specialty pharmacy ... benefit manager Prime Therapeutics LLC (Prime), today officially began ... unveiling of new signage at its headquarters in ... a few other company-owned facilities across the country. This ... of whom will begin to see the AllianceRx Walgreens ...
Breaking Medicine Technology: