Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2000-01-18
2001-11-27
Fredman, Jeffrey (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C424S085100, C435S091200, C514S04400A
Reexamination Certificate
active
06322986
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to predicting the outcome and selecting preferred treatments for colorectal cancer by DNA analysis.
BACKGROUND OF THE INVENTION
Colorectal cancer is a common cancer in the developed world and is a major cause of cancer death. The disease is diagnosed in about 129,400 people and is responsible for nearly 56,600 deaths per year in the United States alone. Traditional therapies for colorectal cancer include surgery, radiation therapy, and chemotherapy, with 5-fluorouracil, levamisole, leucovorin or semustine (methyl CCNU) being the preferred chemotherapeutic agents for colorectal adenocarcinoma.
After surgery or other treatment the ability to predict recurrence and to treat the patient appropriately becomes problematic. Post-surgical treatments have numerous undesired side effects which one wishes to avoid if possible. Conversely, failure to adequately treat any residual tumor cells may result in recurrence of the cancer. Pathological stage, clinical stage, patient age, various protein markers and cell proliferation index are each indicative of the aggressiveness of the cancer and prognostic of eventual outcome. Examples of such indicators may be found in Cohn et al,
Cancer
79:233-44 (1997), Finkelstein et al,
Cancer
71(12):3827-3838 (1993), Harrison et al,
Human Pathology
26(1):31-38 (1995), Furuta et al,
Clinical Cancer Research
4:21-29 (1998), Tanigawa et al,
Cancer Research
57:1043-1046 (1997), Ropponen et al,
Cancer Research
58:342-347 (1998), Wielenga et al,
Cancer Research
53:4754-4756 (1993), Halter et al,
Modern Pathology
5(2):131-134 (1992), Tanabe et al,
Lancet,
341:725-726 (1993), Lanza et al,
Anatomic Pathology
105(5):604-612 (1996), Graham et al,
Modern Pathology
3(3):332-335 (1990), Engel et al,
The American Journal of Surgical Pathology
20(10):1260-1265 (1996), Suzuki et al,
Gastroenterology
109:1098-1104 (1995), Morrin et al,
Gut
35:1627-1631 (1994) and Nakamori et al,
Gastroenterology
106:353-361 (1994).
Colorectal cancer has variable clinical outcome from being cured by surgery or other treatment to recurring with poor prognosis. The potential to predict inoperable cancer, metastatic tumors or simply tumors which require more aggressive treatment has prompted the search for new prognostic markers that would be applied to the colorectal polyp biopsy. Such indicators should prove successful in selecting therapy and predicting disease outcome after diagnosis and before or at any time during treatment. Since severe patient distress can be caused by more aggressive therapy regimens, it is desirable to determine when such therapies are warranted.
For example, patients with a high likelihood of relapse can be treated aggressively with powerful systemic chemotherapy and/or radiation therapy in addition to surgery. When a lesser likelihood of relapse or rapid death is determined, less aggressive therapies can be chosen. It is also desirable to identify those patients who might be candidates for newly developed target-specific therapies such as those described herein.
Unfortunately, following treatment the cancer frequently recurs and sometimes drug resistance develops, particularly in metastatic disease or when diagnosed earlier in life. This results in the tumors eventually regrowing. In such a situation, the tumors are frequently unresponsive to the previous treatment. Furthermore, many metastatic tumors arise in drug-resistive tissues such as the brain, and do not respond to certain chemotherapeutic agents at all.
There is thus a clear need for new assays to predict which tumors would likely respond to particular treatment regimes such as the aforesaid treatment or alternative therapeutic approaches thereby allowing an attending physician to select the most appropriate course of therapy.
A percentage of people are refractory to therapy at the onset. Most respond initially and if they are going to become resistant, developed symptomatic metastases after months or years of drug-based therapy. It is assumed that either new genetic mutations occur in the “dormant” metastatic sites that confers the ability for the tumor to grow again or that clones of drug-independent tumor that were “masked” by the initially faster growing susceptible cells. The resistant tumor cells are then permitted to grow without competition as these susceptible cells are suppressed by the drug therapy.
It has been hypothesized that the use of aggressive chemotherapy early in disease treatment, i.e. in a neoadjuvant approach prior to surgery, may hasten the development of the aggressive clones. Thus, a marker that could predict the “risk” that such a treatment with existing or future chemotherapeutic resistant tumors would be of significant clinical value.
Accordingly, there is a clear need for adjuvant or alternative therapeutic approaches to colorectal tumors and are therefore not fully responsive to surgery. New cancer-specific therapeutic products are currently being developed expanding the spectrum of potential treatments.
Several groups have reported various associations between HER-2
eu (erbB-2)protein, mRNA and gene amplification in various tumor cells as a means for determining cancer stage and outcome. The HER-2
eu gene encodes a cell surface protein similar to the epidermal growth factor (EGF) receptor protein, used to receive growth signals. Cell differentiation has been shown to be of value in determining the prognosis of certain cancers, but this factor does not always correlate to gene amplification or overexpression of erbB-2 in certain gastrointestinal cancers. Kameda et al,
Cancer Research
50:8002-9 (1990) and repeated in Tahara,
Cancer Supplement
75(8):1410-1416 (1995).
Classically, one can determine the prognosis for breast and other hormone-responding related tumors by measuring HER-2
eu amplification and treat the patient with anti-HER-2
eu antibody accordingly. However, in the field of colon cancer a number of researchers have reached divergent and even opposite conclusions regarding levels of protein, mRNA and DNA gene copy numbers of erbB2, also known as HER-2
eu, and also know as p185. For example, Kapitanovic et al,
Gastroenterology
112(4):1103-1113 (1997) suggests a correlation between protein (measured by Western Blot) and colon cancer prognosis. Hu et al,
Chung Hua Chung Liu Tsa Chih
18(4):247-249 (1996) states no correlation exists when measuring protein immunohistochemically. Other cancer systems known to have a correlation between erbB-2 and prognosis don't serve as good models for colon cancer as Caduff et al,
Verh. Desch. Ges. Pathol.
81:219-227 (1997) measured erbB2 immunohistochemically and concluded the molecular mechanisms in endometrial carcinoma (a hormone related cancer) are different from colorectal carcinomas.
Measuring gene amplification (number of copies of the gene) of HER-2
eu (erbB-2) in colon carcinoma has also provided divergent results. Wang et al,
Chung Hua I Hsueh Tsa Chih
74(9):536-538 (1994), found amplification of the gene (by differential PCR) more often in metastatic colon cancer but the difference was not significant. By comparison Knyazev et al,
Oncology
49(2):162-165 (1992) and Tal et al,
Cancer Research
48(6):1517-20 (1988) found only 1 out of 19 and 6 out of 109 colon carcinomas were erbB-2 amplified. Still further Gutman et al,
International Journal of Cancer
44(5):802-5 (1989), found no association between amplification (measured by Southern Blotting) and a specific stage or prognosis. When measuring mRNA, Yang et al,
Anticancer Research
17:1023-1026 (1997), noted an increased level appearing to correlate to certain types of metastasis but not others types of metastasis.
The reason for this divergence of results with colon/colorectal cancer is unclear but different groups use an assortment of different research techniques with different “home brews” of reagents on samples processed in a different manner. One difficulty arises when one measures protein expression instead of gene amplification. Another difficulty ocurrs whe
Albany Medical College
Fredman Jeffrey
Heslin Rothenberg Farley & & Mesiti P.C.
LandOfFree
Method for colorectal cancer prognosis and treatment selection does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for colorectal cancer prognosis and treatment selection, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for colorectal cancer prognosis and treatment selection will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2574896