Abbott Laboratories Corporation

Abbott Molecular Inc.

Rush-presbyterian-st. Luke's Medical Center

Rush University Medical Center

Rush Prebyterian-st. Luke Medical Center

John S Coon

Larry E Morrison

R Martin Emanuele

Mannarsamy Balasubramanian

Dimitri Semizarov

Xin Lu

Ke Zhang

Rick R Lesniewski

Himanshu Shah

Dimitri Seminarov

Susan S Jewell

The present disclosure provides methods for identifying early stage non-small-cell lung cancer (NSCLC) patients who will have an unfavorable prognosis for the recurrence of lung cancer after surgical resection. The methods are based in part on the discovery of chromosomal copy number abnormalities that can be used for prognostic classification. The methods preferably use fluorescence in situ hybridization with fluorescently labeled nucleic acid probes to hybridize to patient samples to quantify the chromosomal copy number of these genetic loci.

Diagnostic methods for determining prognosis of non-small cell lung cancer

The invention provides methods for identifying early stage non-small cell lung cancer (NSCLC) patients who will have a favorable prognosis for the recurrence of lung cancer after surgical resection. The invention is based on the discovery that assessment of chromosomal copy number abnormalities at two or more of chromosome 5p15, 7p12, 8q24 and centromere 6 can be used for prognostic classification. The invention preferably uses fluorescence in situ hybridization with fluorescently labeled nucleic acid probes to hybridize to patient samples to quantify the chromosomal copy number of the these genetic loci. Assessment of the copy number abnormality patterns using four classifiers produced statistically significant prognostic classification for NSCLC: (i) the Range3 pattern of cells showing a difference on a cell by cell basis, of at least three FISH probe signals between the FISH signals at the chromosomal locus with the largest number of FISH signals minus the FISH signals at the chromosomal locus with the lowest number of FISH signals; (ii) the MYC/EGFR % loss pattern assessing the percentage of cells showing fewer MYC FISH probe signals than EGFR FISH probe signals; (iii) a combination of the Range3 pattern and the MYC/CEP6 ratio pattern of a percentage of cells showing a relative loss of MYC FISH probe signals to the FISH probe signal for CEP6; (iv) the combination of the MYC/5p15 ratio pattern showing the relative ratio of MYC and 5p15 locus signals of &#x2265;0.80 and the 5p15/CEP6 ratio pattern assessing percentage of cells having a relative ratio of 5p15 FISH probe signals to CEP6 FISH probe signals &#x2265;1.1 versus MYC/5p15 ratio of &#x3c;0.80 or 5p15/CEP6&#x3c;1.1; and (v) a combination of the average range of probe signal differences of equal to or greater than about 2.5 with the Range3 pattern in a percentage of the cells. The invention can be used to identify those early stage NSCLC patients at higher risk of recurrence who should be treated with neoadjuvant chemotherapy before surgery or with adjuvant chemotherapy after surgery.

Disclosed are methods for identifying early-stage non-small-cell lung cancer (NSCLC) patients who will have an unfavorable prognosis for the recurrence of lung cancer after surgical resection. The methods are based in part on the discovery that chromosomal copy number gains at Chr19, 34.7 Mb-35.6 Mb can be used for prognostic classification. The methods preferably use fluorescence in situ hybridization with fluorescently labeled nucleic acid probes to hybridize to patient samples to quantify the chromosomal copy number of this genetic locus.

The invention provides methods for identifying early stage non-small cell lung cancer (NSCLC) patients who will have a favorable prognosis for the recurrence of lung cancer after surgical resection. The invention is based on the discovery that assessment of chromosomal copy number abnormalities at two or more of chromosome 5p15, 7p12, 8q24 and centromere 6 can be used for prognostic classification. The invention preferably uses fluorescence in situ hybridization with fluorescently labeled nucleic acid probes to hybridize to patient samples to quantify the chromosomal copy number of the these genetic loci. Assessment of the copy number abnormality patterns using four classifiers produced statistically significant prognostic classification for NSCLC: (i) the Range3 pattern of cells showing a difference on a cell by cell basis, of at least three FISH probe signals between the FISH signals at the chromosomal locus with the largest number of FISH signals minus the FISH signals at the chromosomal locus with the lowest number of FISH signals; (ii) the MYC/EGFR % loss pattern assessing the percentage of cells showing fewer MYC FISH probe signals than EGFR FISH probe signals; (iii) a combination of the Range3 pattern and the MYC/CEP6 ratio pattern of a percentage of cells showing a relative loss of MYC FISH probe signals to the FISH probe signal for CEP6; (iv) the combination of the MYC/5p15 ratio pattern showing the relative ratio of MYC and 5p15 locus signals of &#x2267;0.80 and the 5p15/CEP6 ratio pattern assessing percentage of cells having a relative ratio of 5p15 FISH probe signals to CEP6 FISH probe signals &#x2267;1.1 versus MYC/5p15 ratio of &#x3c;0.80 or 5p15/CEP6&#x3c;1.1; and (v) a combination of the average range of probe signal differences of equal to or greater than about 2.5 with the Range3 pattern in a percentage of the cells. The invention can be used to identify those early stage NSCLC patients at higher risk of recurrence who should be treated with neoadjuvant chemotherapy before surgery or with adjuvant chemotherapy after surgery.

The invention provides methods for identifying early stage non-small cell lung cancer (NSCLC) patients who will have a favorable prognosis for the recurrence of lung cancer after surgical resection. The invention is based on the discovery that assessment of chromosomal copy number abnormalities at chromosome 10q23.3 and centromere 10 can be used for prognostic classification. The invention preferably uses fluorescence in situ hybridization with fluorescently labeled nucleic acid probes to hybridize to patient samples to quantify the chromosomal copy number of the these genetic loci. The chromosome copy number can also be determined using, for example, PCR or array CGH. Assessment of the copy number abnormality patterns with a classifier based on the relative loss of 10q23.3 signals compared to the centromere 10 signals produced statistically significant prognostic classification for NSCLC. The ratio of PTEN/CEP 10 signals, using a cutoff of 0.80, was capable of dividing patients into a group of 41 (&#x2267;0.80) in which 33 (80.5%) had the favorable prognosis, and a group of 18 (&#x3c;0.80) in which 6 (33.3%) had the favorable prognosis (p=0.0008). Median times to recurrence in the former and latter groups were 83.0 and 13.0 months, respectively (p&#x3c;0.0001).

Prognostic test for early stage non small cell lung cancer (NSCLC)

The present invention provides methods for identifying cancer patients susceptible to effective treatment with trastuzumab and other medications that function similarly to trastuzumab. The invention is based on the discovery that certain chromosomal abnormalities can be used to selectively identify cancer patients that are likely to be successfully treated with medication that inhibits the signaling capability of the HER-2 receptor protein or otherwise function similarly to trastuzumab. The invention is based on the use of nucleic acid technology where nucleic acid probes are allowed to hybridize to cell samples and the number of copies of particular genetic regions quantified. The present invention also provides kits and sets of probes for use in identifying cancer patients susceptible to effective treatment with trastuzumab and other medications that function similarly to trastuzumab.

Methods of identifying patients for treatment with HER-2/neu inhibitors based on detection of HER-2/neu and TOP2A gene copy number

The present invention comprises methods and compositions for reducing or eliminating multidrug resistance in cancers or certain infections by drug resistant microorganisms in patients. According to the method and composition of the present invention, a non-ionic amphipathic diester of fatty acids or a reverse poloxmer is administered to a patient in which a cancer or microorganism exhibits multidrug resistance to the chemotherapeutic agent. The method and composition of the present invention may be employed with particular efficacy where multidrug resistance to any chemotherapeutic agent has been conferred upon a cancer.

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Oak Park, IL, United States of America

John S Coon