Compositions and methods for treating cancer

#The present disclosure relates generally to methods for treating small-cell lung cancer (SCLC) and neuroblastoma using inhibitors of ONECUT2. The present disclosure also relates generally to methods for treating cancer, wherein the cancer is selected from the group consisting of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), adenocarcinoma (AC), and combinations thereof.

#Patients diagnosed with small cell lung cancer generally have a poor prognosis. As such, there remains a need for compositions and methods for treating small cell lung cancer. There is also a need in the art for compositions and methods for treating neuroblastoma.

#Patients diagnosed with large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) generally have a poor prognosis. As such, there remains a need for compositions and methods for treating large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC).

#Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.

#FIG. 1 depicts in accordance with various embodiments of the invention, ONECUT2 RNA expression is highest in small cell lung cancer (SCLC) and neuroblastoma cell lines. The box highlights data from 53 SCLC and 17 neuroblastoma cell lines. Y-axis is log 2 mRNA expression level. From the Cancer Cell Line Encyclopedia (www.broadinstitute.org).

#FIG. 2 depicts in accordance with various embodiments of the invention, ONECUT2 expression is highest in SCLC clinical samples relative to normal lung or other lung tumors.

#All references cited herein are incorporated by reference in their entirety as though fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Allen et al., Remington: The Science and Practice of Pharmacy 22nd ed., Pharmaceutical Press (Sep. 15, 2012); Hornyak et al., Introduction to Nanoscience and Nanotechnology, CRC Press (2008); Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology 3rd ed., revised ed., J. Wiley & Sons (New York, N.Y. 2006); Smith, March's Advanced Organic Chemistry Reactions, Mechanisms and Structure 7th ed., J. Wiley & Sons (New York, N.Y. 2013); Singleton, Dictionary of DNA and Genome Technology 3rd ed., Wiley-Blackwell (Nov. 28, 2012); and Green and Sambrook, Molecular Cloning: A Laboratory Manual 4th ed., Cold Spring Harbor Laboratory Press (Cold Spring Harbor, N.Y. 2012), provide one skilled in the art with a general guide to many of the terms used in the present application. For references on how to prepare antibodies, see Greenfield, Antibodies A Laboratory Manual 2nd ed., Cold Spring Harbor Press (Cold Spring Harbor N.Y., 2013); Köhler and Milstein, Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion, Eur. J. Immunol. 1976 Jul, 6(7):511-9; Queen and Selick, Humanized immunoglobulins, U.S. Pat. No. 5,585,089 (1996 Dec); and Riechmann et al., Reshaping human antibodies for therapy, Nature 1988 Mar. 24, 332(6162):323-7.

#For references on pediatrics, see Schwartz et al., The 5-Minute Pediatric Consult 4th ed., Lippincott Williams & Wilkins, (Jun. 16, 2005); Robertson et al., The Harriet Lane Handbook: A Manual for Pediatric House Officers 17th ed., Mosby (Jun. 24, 2005); and Hay et al., Current Diagnosis and Treatment in Pediatrics (Current Pediatrics Diagnosis & Treatment) 18thed., McGraw-Hill Medical (Sep. 25, 2006).

#One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, various features of embodiments of the invention. Indeed, the present invention is in no way limited to the methods and materials described. For convenience, certain terms employed herein, in the specification, examples and appended claims are collected here.