In new research, scientists have tested a new precision medicine approach –OncoTreat therapy— to treat metastatic pancreatic cancer. Using the new approach, the team studied the RNA; the tissue-specific copy of a cancer cell’s DNA, rather than the DNA itself. This will give a much more accurate picture of the genetic programs operating inside a tumor that enable its survival.
Pancreatic ductal carcinoma (PDA)–the most common form of pancreatic cancer. Researchers have identified few genetic drivers in pancreatic tumors, and the most common driver (KRAS) is not easily targeted. Conservatively, only about 15% of PDA patients are likely to benefit from conventional DNA mutation-based precision medicine therapies and most of these will either not respond or will relapse with a drug-resistant form of the disease.
Instead of looking at the mutations encoded in a tumor's DNA, the team analyze the tumor's RNA. Since RNA is the tissue-specific working copy of a cancer cell's DNA, it's a more accurate reflection of the genetic programs that are active in a tumor and critical for its survival. The patients then can match the patient to approved and investigational drugs that inhibit those programs.
In preliminary tests of this approach–called OncoTreat–on PDA tumor samples, the researchers identified at least one matching drug for 85% of patients. The approach has also been tested on other cancers and is the first NYS Department of Health CLIA approved RNA-based test to match patients to the full repertoire of FDA-approved and investigational drugs in phase 2 and phase 3 clinical trials. To date, three of four patients who received OncoTreat therapy have exhibited clinical responses.
OncoTreat identifies drugs that can invert the activity of a novel class of cryptic cancer targets, called master regulator proteins. These proteins, which are conserved within large subsets of cancer patients and are responsible for integrating the effect of individual genomic alterations and for making the cancer cell impervious to a wide range of perturbations, including those resulting from conventional drug treatment. By targeting the 'engine room' of the cancer cell, the team hope to develop more universal and more effective treatment.
PDA is a highly lethal disease with no truly effective treatment options. New approaches to this disease are desperately needed. The primary goal of the phase 1b clinical trial is to assess anti-cancer activity of OncoTreat-predicted drugs in 30 patients with recurrent PDA, on an individual patient basis. The grant will also support preclinical studies to develop optimized two-drug regimens for groups of PDA patients based on their OncoTreat profile.