Methods of determining cancer therapy effectiveness

A method of determining if one or more antibody-based therapies selected from anti-Her2, anti-Nectin-4, and anti-TROP2 antibody-based therapy is likely to be effective for treating a tumor in a subject, comprising:

• a. measuring the expression level of Her2, Nectin-4, and TROP2 in a tumor sample obtained from the subject;
• b. measuring the expression level of at least one housekeeping gene selected from CIAO1, EIF2B1, and HMBS in the tumor sample;
• c. normalizing the expression levels of Her2, Nectin-4, and TROP2 to the at least one housekeeping gene to obtain normalized expression levels of the one or more gene products;
• and
• d. determining that anti-Her2, anti-Nectin-4, or anti-TROP2 antibody-based therapy is likely to be effective if the normalized expression levels of Her2, Nectin-4, or TROP2 are above a threshold level.

A method of treatment of a subject with a therapy likely to be effective, comprising administering to said subject the therapy, wherein the therapy has been identified as likely to be effective by a method comprising:

• a. measuring the expression level of a gene products associated with the therapy from a biological sample obtained from the subject, wherein the sample comprises nucleic acids derived from cells targeted by the therapy;
• b. measuring the expression level of at least one housekeeping gene selected from CIAO1, EIF2B1, and HMBS in the biological sample;
• c. normalizing the expression levels of the gene product to the at least one housekeeping gene to obtain a normalized expression level of the gene product;
• and
• d. determining that the therapy is likely to be effective for treating the subject if the normalized expression level of the gene product is above a threshold level,
• wherein the therapy comprises an antibody, bispecific antibody, antibody-drug conjugate, antibody fragment, radiopharmaceutical, Car-T cell, or engineered T cell receptor.

A method of treatment of a subject with an antibody-based therapy identified as most likely to be effective selected from anti-Her2, anti-Nectin-4, and anti-TROP2 antibody-based therapy, comprising administering to said subject the antibody-based therapy identified as most likely to be effective, wherein the antibody-based therapy has been identified as most likely to be effective by a method comprising:

• a. measuring the expression level of Her2, Nectin-4, and TROP2 in a tumor sample obtained from the subject;
• b. measuring the expression level of at least one housekeeping gene selected from CIAO1, EIF2B1, and HMBS in the tumor sample;
• c. normalizing the expression levels of Her2, Nectin-4, and TROP2 to the at least one housekeeping gene to obtain normalized expression levels of the one or more gene products;
• d. determining that anti-Her2, anti-Nectin-4, or anti-TROP2 antibody-based therapy is likely to be effective if the normalized expression levels of Her2, Nectin-4, or TROP2 are above a threshold level;
• and
• e. determining which antibody-based therapy is more likely to be effective based on having the highest relative expression of the associated gene product over the associated threshold level.