In-vivo methods and kits for detecting presence of a combination of biomarkers indicating colorectal cancer are described. One of the methods includes inserting into a patient a combination of binding agents comprising one binding agent having high affinity to CEACAM5 and at least one binding agent having high affinity to at least one of two biomarkers selected from Olfactomedin 4- (OLFM4) and S100P. The method further includes inserting into the patient an in-vivo sensing device, detecting an optical change using the in-vivo sensing device, which occurs when at least one of the combination of binding agents binds to at least one of the corresponding combination of biomarkers, and determining, based on the optical change, presence of colorectal cancer in the patient.