Methods for predicting and treating chemoresistance in small cell lung cancer patients
OwnerÁlvaro D. Quintanal Villalonga, Charles Michael Rudin +1inventors
InventorsÁlvaro D. Quintanal Villalonga, Charles Michael Rudin, John Thomas Poirier
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Abstract
The present disclosure relates to methods for detecting chemoresistant SCLC tumors in a patient and/or methods for determining whether a patient diagnosed with small cell lung cancer (SCLC) will benefit from treatment with chemotherapy. These methods are based on screening a SCLC patient for elevated XP01 expression. The present technology also provides methods for sensitizing SCLC patients to chemotherapy using an inhibitor of XP01.
Claims26
A method for selecting a small cell lung cancer (SCLC) patient that has received or is receiving chemotherapy for treatment with an XPO1 inhibitor comprising
- (a) detecting the presence of at least one mutation that results in elevated expression or activity of exportin-1 in a biological sample obtained from the SCLC patient;
- and
- (b) administering an effective amount of an XPO1 inhibitor to the SCLC patient,
- wherein the chemotherapy comprises a topoisomerase inhibitor, optionally wherein
- the XPO1 inhibitor is separately, sequentially or simultaneously administered with the chemotherapy;
- or
- the biological sample obtained from the SCLC patient comprises biopsied tumor tissue, whole blood, plasma, or serum.
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A method for sensitizing a SCLC patient to chemotherapy comprising
- administering to the SCLC patient an effective amount of an XPO1 inhibitor separately, sequentially or simultaneously with the chemotherapy, wherein the chemotherapy comprises a topoisomerase inhibitor, and
- wherein the SCLC patient comprises at least one mutation that results in elevated expression or activity of exportin-1, optionally wherein the at least one mutation is detected in a biological sample obtained from the SCLC patient;
- or
- wherein mRNA and/or polypeptide expression and/or activity levels of exportin-1 in a biological sample obtained from the SCLC patient are elevated compared to that observed in a control sample obtained from a healthy subject or a predetermined threshold,
- optionally wherein the biological sample obtained from the SCLC patient comprises biopsied tumor tissue, whole blood, plasma, or serum.
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A kit comprising an XPO1 inhibitor, one or more chemotherapeutic agents, and instructions for treating SCLC.
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Dependencies are inferred from the claim text.