Promising new OVC research on Gene Sequencing
Elsevier Global Medical News. 2010 Nov 16, J Smith
Mutational analysis using a Sequenom-based technique of ovarian cancer samples has unveiled more mutations than were previously known, and could become part of a personalized standard of care for these difficult-to-treat cancers, according to investigators.
Dr. Ursula Matulonis of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, plans to elaborate on the findings Nov. 17 at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin.
For their research, Dr. Matulonis and her colleagues subjected samples from high-grade serous ovarian cancers (stage III or IV) without known BRCA mutations to the technique, which is called OncoMap.
OncoMap uses spectronomic gene sequencing to identify more than 1,100 mutations on 114 oncogenes. It works using fresh-frozen or formalin-fixed paraffin embedded (FFPE) tissue samples; Dr. Matulonis' team used FFPE samples only.
The team, testing 203 samples with OncoMap, found mutations of 50 genes in total. Some mutations were in genes previously identified in ovarian cancer, including KRAS, CTNNB1, and PIK3CA. Others were not previously known to occur in this disease, but, importantly, are potential drug targets with existing agents.
"It's not like HER2 in breast cancer where that is found in about 30% of breast cancers - we found many mutations in the ovarian cancer samples and they were infrequent," Dr. Matulonis said in a telephone interview prior to the conference; she noted, however, that OncoMap identified KRAS and PIK3CA mutations as the most common, occurring in about 25% of tumors, and "that was reassuring," as it was in line with expectations.
While many of the additional mutations were found in lower frequency, "we can still increase treatment options, as we get smarter with drugs," said Dr. Matulonis, medical director of gynecologic oncology at Dana-Farber,
She said she has already referred ovarian cancer patients to clinical trials based on OncoMap results and hopes to refer more for personalized drug treatments. For example, XL147 and GDC-0941, novel inhibitors of P13 kinase mutations, are in clinical trials; ovarian cancer patients with these mutations could be enrolled in those trials. Similarly, if an ovarian cancer were shown to exhibit an ALK alteration, the patient could be treated with a drug that targets that protein.
Dr. Matulonis' team is now using OncoMap on all new ovarian cancers, including nonserous cancers, diagnosed at Dana-Farber, and she predicted the test will become standard in clinical practice within 6 months to a year.
The investigators disclosed funding for the study from Madeline Franchi Ovarian Cancer Research Fund, twoAM Fund and the Sally Cooke Ovarian Cancer Research Fund.
Comments
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If I Understand
Good Morning,
So, if I understand correctly, there are many more tumor mutations for ovarian cancer, then there is for breast cancer, which would explain the fact that many more women survive breast cancer from treatment and early detection. They have less mutations and as a whole more women with breast cancer have the same mutation. So, if you have ovarian cancer, they are trying to determine the mutation type and treat it accordingly. That might explain why we all get the same treatment and some of us respond better then others and also the extent of the cancer. Did I get it right? Deep thinking and very interesting. Thank-You, Paula0 -
Gene Sequencingcancer survivor x 4 said:If I Understand
Good Morning,
So, if I understand correctly, there are many more tumor mutations for ovarian cancer, then there is for breast cancer, which would explain the fact that many more women survive breast cancer from treatment and early detection. They have less mutations and as a whole more women with breast cancer have the same mutation. So, if you have ovarian cancer, they are trying to determine the mutation type and treat it accordingly. That might explain why we all get the same treatment and some of us respond better then others and also the extent of the cancer. Did I get it right? Deep thinking and very interesting. Thank-You, Paula
Academics are besides themselves over the promise of gene sequencing. It seems so cool that it simply must be good for something. How about in the area of identifying drugs which will work in individual patients? All DNA or RNA-type tests are based on "population" research (not individuals). They base their predictions on the fact that a higher percentage of people with similar genetic profiles or specific mutations may tend to respond better to certain drugs. This is not really "personalized" medicine, but a refinement of statistical data. The NCI has concluded (J Natl Cancer Inst. March 16, 2010), gene-guided chemotherapy (gene signatures) cannot determine treatment plans for patients. It cannot test sensitivity to any of the targeted therapies. It just tests for "theoretical" candidates for targeted therapy.0
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