Methods and compositions for identifying and treating patients with small cell lung cancer
Described herein are methods and compositions useful in detecting, diagnosing and treating small cell lung cancer. Transgenic animal models and cell lines are disclosed for the study of a small cell lung cancer subtype. Methods of screening and identifying active agents for the treatment of a small cell lung cancer subtype as well as methods of identifying patients susceptible to treatment with aurora kinase inhibitors are also provided.
1. A method of detecting a variant subtype of small cell lung cancer in a subject and treating the subject, the method comprising:
a. obtaining or having obtained a sample from a human subject;
b. determining the level of (i) NEUROD1, (ii) Myc or Mycl, and (iii) ASCL1 in the subject's sample;
c. detecting an increased level of NEUROD1, an increased level of Myc or a decreased level of Mycl and a decreased level of ASCL1 in the subject's sample as compared to a sample from a human subject that does not have small cell lung cancer, thereby detecting a variant subtype of small cell lung cancer in the subject; and
d. administering to the subject determined to have the variant subtype of small cell lung cancer an aurora kinase inhibitor.
2. The method of claim 1 , wherein the level of (i) NEUROD1, (ii) Myc or Mycl, and (iii) ASCL1 is determined using RNA-sequence data analysis or polymerase chain reaction.
3. The method of claim 2 , wherein the sample is a blood or lung tissue sample.
4. A method of predicting a small cell lung cancer patient's responsiveness to an aurora kinase inhibitor and treating the patient, the method comprising:
a. obtaining or having obtained a sample from the patient;
b. determining the level of (i) NEUROD1, (ii) Myc or Mycl, and (iii) ASCL1 in the patient's sample,
c. detecting an increased level of NEUROD1, an increased level of Myc or a decreased level of Mycl and a decreased level of ASCL1 in the patient's sample as compared to a sample from a human subject that does not have small cell lung cancer, thereby indicating that the patient is likely to respond to an aurora kinase inhibitor, and
d. following step c., administering to the patient an aurora kinase inhibitor.
5. A method of predicting a small cell lung cancer patient's responsiveness to a BCL-2 inhibitor and treating the patient, the method comprising:
a. obtaining or having obtained a sample from the patient;
b. determining the level of (i) NEUROD1, (ii) Myc or Mycl, and (iii) ASCL1 in the patient's sample,
c. detecting a decreased level of NEUROD1, an increased level of Mycl or a decreased level of Myc, and an increased level of ASCL1 in the patient's sample as compared to a sample from a human subject that does not have small cell lung cancer, thereby indicating that the patient is likely to respond to a BCL-2 inhibitor; and d. following step c., administering to the patient a BCL-2 inhibitor.
6. The method of claim 1 , wherein the aurora kinase inhibitor is alisertib.
7. The method of claim 4 , wherein the aurora kinase inhibitor is alisertib.