Treating basal-like genotype cancers
Provided herein are methods of treating a subject with cancer comprising administering to the subject a death receptor agonist. Also provided herein are methods of screening a breast cancer cell for responsiveness to a DR5 agonist. Further provided herein are antibodies that selectively bind an N-terminal CARD of DDX3, a DDX3 lacking an N-terminal CARD, and an 80 kDa baculovirus TAP repeat (BIR).
1. A method of treating a subject with cancer, the method comprising:
(a) selecting a subject with a breast cancer, wherein the breast cancer is a basal-like genotype cancer and is HER2 non-amplified, and wherein the breast cancer shows reduced levels of DR5/DDX3/cIAP1 complex as compared to a control; and
(b) administering to the subject a death receptor agonist, wherein the death receptor agonist is a DR5 agonist.
2. The method of claim 1 , wherein the DR5 agonist is an antibody.
3. The method of claim 1 , wherein the breast cancer is estrogen receptor negative (ER negative), progesterone receptor negative (PR negative), or both ER negative and PR negative.
4. The method of claim 1 , wherein the levels of DR5/DDX3/cIAP1 complex are detected using a whole cell lysate assay.
5. The method of claim 1 , wherein the breast cancer comprises a DDX3 lacking a functional N-terminal CARD.
6. The method of claim 5 , wherein the DDX3 lacking a functional N-terminal CARD has a truncated or deleted N-terminal CARD.
7. The method of claim 1 , wherein the breast cancer is resistant to a chemotherapeutic agent in the absence of the death receptor agonist.
8. The method of claim 7 , wherein the breast cancer is resistant to adriamycin.
9. The method of claim 7 , wherein the breast cancer is resistant to paclitaxel.
10. The method of claim 7 , wherein the breast cancer is resistant to cisplatin or carboplatin.
11. The method of claim 7 , further comprising administering to the subject the chemotherapeutic agent.
12. The method of claim 11 , wherein the chemotherapeutic agent is administered intravenously every three weeks.
13. The method of claim 1 , wherein the death receptor agonist is administered at three week, two week, or one week intervals.