Selective inhibitors of tumor-initiating cells

26-28. (canceled)

The method of claim 27, wherein if the cancer is classified as having a poor prognosis or being a malignant cancer, the method further comprises the step of administering at least one proteasome inhibitor to the subject.

A method of classifying a cancer in a subject in need thereof, the method comprising:

• a. assaying expression of at least five biomarkers set forth in SEQ ID NOs:
• 1-4, 6, 7, 13, 14, 23, 29, 33-35, 37, 38, 66, 72, 77, 78, 84, 91, 93, and 151 in a biological sample obtained from the subject having a cancer, and
• b. comparing the expression of the five or more of the 23 malignancy associated response signature biomarkers in the biological sample obtained from the subject having a cancer with a reference value, wherein increased expression of 1.8-fold or greater of at least ten of the biomarkers in the biological sample obtained from the subject relative to the reference value indicates that the cancer is classified as having a poor prognosis or being a malignant cancer, and absence of increased expression of 1.8-fold or greater of at least ten of the biomarkers relative to the reference value indicates that the cancer does not have poor prognosis or is not a malignant cancer.

43-46. (canceled)

The method of claim 46, wherein the at least one proteasome inhibitor specifically inhibits the malignancy associated response signature biomarker set forth in SEQ ID NOs:

• 134 (MCL-1).

The method of claim 46, wherein the at least one proteasome inhibitor is an siRNA or antisense RNA agent.

The method of claim 46, wherein the at least one proteasome inhibitor is bortezomib.

A method of classifying a cancer in a subject in need thereof, the method comprising:

• a. assaying expression of at least three malignancy associated response signature biomarkers set forth in SEQ ID NOs:
• 1, 2, 4, 7, 15, 16, 21, 29, 33, 34, 38, 60, 74, 76, and 149 in a biological sample obtained from the subject having a cancer, and
• b. comparing the expression of the at least three malignancy associated response signature biomarkers in the biological sample obtained from the subject having a cancer with a reference value, wherein increased expression of 1.8-fold or greater of at least three of the biomarkers in the biological sample obtained from the subject relative to the reference value indicates that the cancer is classified as having a poor prognosis or being a malignant cancer, and absence of increased expression of 1.8-fold or greater of at least three of the biomarkers relative to the reference value indicates that the cancer does not have poor prognosis or is not a malignant cancer.

55-56. (canceled)

(canceled)

67-68. (canceled)

89-101. (canceled)

A method of identifying a candidate therapeutic agent against a cancer initiating cell comprising the step of

• a. exposing a BPLER cell culture to a test agent, wherein said BPLER cell culture comprises human breast primary epithelial cells (BPE) transformed with a defined set of genetic elements;
• b. measuring expression of at least ten of the 154 malignancy associated response signature biomarkers of claim 1 in the culture,
• c. comparing the expression of the same at least 10 biomarkers of malignancy associated response signature biomarkers of claim 1 as was measured in step (b) to an expression signature reference from a BPLER cell culture that has not been exposed to the test agent, wherein a decrease of expression of at least 5 of the at least 10 genes in the test culture compared to the expression signature reference indicates that the test agent is a candidate therapeutic agent against a cancer initiating cell.

103-105. (canceled)