Friday, January 14, 2011
full free text: Targeted Epigenetic Therapies: The Next Frontier? — J. Natl. Cancer Inst. (includes discussion regarding clear cell/ARIDIa mutation
Targeted Epigenetic Therapies: The Next Frontier?
1. Rabiya S. Tuma
When researchers look for mutations associated with cancer, they often expect to come up with alterations in signaling molecules or transcription factors. But an increasing number of the mutations found are in genes that regulate the epigenome—a system that alters DNA structure and regulates gene activity without changing the nucleotide sequence itself.
On Sept. 8, investigators published two independent reports online—one in Science and one in the New England Journal of Medicine—showing that mutations in an epigenetic regulatory gene, ARID1a, were associated with approximately half of the ovarian clear-cell cancers tested.
Randomized Phase III Clinical Trial Evaluating Weekly Cisplatin for Advanced Epithelial Ovarian Cancer
"Thus, increasing dose intensity of cisplatin does not improve PFS or OS compared with standard chemotherapy."
High-grade, chemotherapy-resistant ovarian carcinomas overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy (RNA/IL-2/Adecatumumab)
AbstractOBJECTIVE: We evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the potential of MT201 (adecatumumab), a human-monoclonal-antibody that targets EpCAM against chemotherapy-resistant ovarian disease.
STUDY DESIGN: EpCAM expression was evaluated by real-time polymerase chain reaction and flow cytometry. Sensitivity to MT201 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in 4-hour chromium-release assays. The effect of interleukin-2 on MT201 ADCC was also studied.
RESULTS: High messenger RNA expression by real-time polymerase chain reaction and high EpCAM surface expression by flow cytometry was detected in 71% of ovarian cancers (5 of 7 cell lines). Although these cell lines were highly resistant to complement-dependent cytotoxicity and natural killer-dependent cytotoxicity in vitro (range of killing, 0-7%), EpCAM-positive cell lines showed high sensitivity to MT201 ADCC (range of killing, 27-66%). Incubation with interleukin-2 further increased the cytotoxic activity against EpCAM-positive ovarian cancer cell lines.
CONCLUSION: MT201 may represent a novel, potentially highly effective treatment option for patients with ovarian carcinoma whose body is harboring disease refractory to chemotherapy.
Perspectives 2011: Key to Ovarian Cancer Detection - the Endocrine Society Research Affairs Endocrine News Jan 2011 Dr Lee (Chicago)
Perspective: Dr Lee (Chicago)
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Annual Costs of Cancer Care | Cancer Prevalence and Cost of Care Projections - female/male cancer sites (ncluding ovarian)
Chart: Average Annual Costs of Care
Annualized Mean Net Costs of Care by Age, Gender and Phase of Care (Per Patient). Costs in 2010 US Dollars.
- 18.1 million cancer survivors in 2020, 30% more than 2010
- Costs of cancer care: $157 billion in 2010 dollars
- Growth and aging of the U.S. population is the primary cause
Create Your Own ChartGraph by Cancer Site and Phase of Cancer
(See cost of care or prevalence for cancer site, sex, age and year under various assumptions)
Projection Tables for 2020National Expenditures for Cancer Care
Base DataAverage Annual Costs of Care
"....Statistical modeling, of course, depends on the assumptions used by the researchers — so check out the full study to see those details. And here’s an interactive tool that allows you to change some of the assumptions."
excerpt/also see Table 5 for projection (cost) estimates:
Recent and Projected Incidence
For most of the cancer sites, incidence has been decreasing, and we estimated a negative annual percent change (Table 1) during the period 1996–2005. The largest decreases in men were for lung, stomach, and colorectal cancers, respectively, −2.72, −2.24, and −2.22 annual percent change in age-adjusted rates. More dramatic decreases were observed for women for ovarian and cervical cancer, −4.71 and −3.95, respectively, annual percent change in age-adjusted rates. Incidence of kidney cancer and melanoma has been increasing in both men and women, and incidence of lymphoma and brain cancer has been increasing in women (Table 1). Among the five major cancer sites, the largest decreases in incidence were observed for lung and colorectal cancers in men, −2.72 and −2.22, respectively, annual percent change in age-adjusted incidence rates (Figure 1; Similar figures for more cancer sites are available at http://costprojections.cancer.gov.).
View this table:
Incidence and survival trends used in the incidence and survival trend scenario*