Methods and systems for determination of an effective therapeutic regimen and drug discovery

A method of determining risk for developing resistance or monitoring the further development of resistance to a first therapeutic agent in an ER+ breast cancer patient comprising:

• a) obtaining a biological sample and a tumor sample from the patient;
• b) contacting the biological sample and the tumor sample from the patient with a probe that binds to a region of a sequence in a gene associated with kinase phosphorylation to identify at least one mutation,
• wherein binding of the probe with the biological sample but not the tumor sample is indicative of a tumor that is at risk for developing resistance to a therapeutic agent;
• c) using a pattern matching algorithm to determine if the at least one mutation is an activation mutation or a resistance mutation;
• and
• d) using the pattern matching algorithm and a crystal structure library to identify therapeutic agents to target the activation mutation or resistance mutation, thereby identifying the risk for developing resistance or monitoring the further development of resistance to the first therapeutic agent optionally administering the first therapeutic agent to the patient and optionally repeating steps a) and b) at different time points in the patient's treatment.