Treatment Of Pan-Cancer Phenotype With Regulator of Telomere Elongation Helicase 1 (RTEL1) Inhibitors

A method of treating a subject having a pan-cancer phenotype or at risk of developing a pan-cancer phenotype by administering a pan-cancer phenotype therapeutic agent, the method comprising:

• determining or having determined whether the subject has a Regulator of Telomere Elongation Helicase 1 (RTEL1) variant nucleic acid molecule, by:
• obtaining or having obtained a biological sample from the subject;
• and
• performing or having performed a sequence analysis on the biological sample to determine if the subject has a genotype comprising an RTEL1 variant nucleic acid molecule;
• and
• administering or continuing to administer the pan-cancer phenotype therapeutic agent in an amount that is the same as or less than a standard dosage amount, and/or an RTEL1 inhibitor to a subject that is RTEL1 reference;
• administering or continuing to administer the pan-cancer phenotype therapeutic agent in an amount that is the same as or less than a standard dosage amount, and/or an RTEL1 inhibitor to a subject that is heterozygous for the RTEL1 variant nucleic acid molecule;
• or
• administering or continuing to administer the pan-cancer phenotype therapeutic agent in a standard dosage amount to a subject that is homozygous for the RTEL1 variant nucleic acid molecule;
• wherein the presence of the RTEL1 variant nucleic acid molecule indicates the subject has a decreased risk of developing pan-cancer phenotype;
• and
• wherein the pan-cancer phenotype comprises adrenal cancer, bladder cancer, bone cancer, cartilage cancer, brain cancer, breast cancer, cervical cancer, colon cancer, esophagus cancer, kidney cancer, oral cavity cancer, pharynx cancer, liver cancer, lung cancer, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, testicular cancer, thyroid cancer, or blood cancer.

A method of identifying a subject having an increased risk of developing a pan-cancer phenotype, the method comprising:

• determining or having determined the presence or absence of a Regulator of Telomere Elongation Helicase 1 (RTEL1) variant nucleic acid molecule in a biological sample obtained from the subject;
• wherein:
• when the subject is RTEL1 reference, then the subject has an increased risk of developing the pan-cancer phenotype;
• and
• when the subject is heterozygous or homozygous for the RTEL1 variant nucleic acid molecule, then the subject has a decreased risk of developing the pan-cancer phenotype.