Abstract: Aspects of the technology described herein are directed to a method of treating gastrointestinal cancer in a subject. This method involves selecting a subject, where the subject (i) has been diagnosed with a gastrointestinal cancer and (ii) has (a) a pathogenic mutation in one or more homologous recombination-DNA damage repair (HR-DDR) pathway genes and/or (b) a family history suggestive of a breast or ovarian cancer syndrome; and administering to the subject an effective amount of a Poly(ADP ribose) polymerase (PARP) inhibitor, in combination with oxaliplatin and an antimetabolite. Methods of treating a gastrointestinal tumor in a subject and of increasing sensitivity of gastrointestinal tumor cells to oxaliplatin are also disclosed.