The PACT test, which stands for Profiling of Actionable Cancer Targets, is a sophisticated molecular diagnostic tool used in oncology to personalize cancer treatment. This test utilizes advanced genetic sequencing technology to analyze specific DNA changes within a patient’s tumor. It identifies alterations in hundreds of genes simultaneously, providing a comprehensive genomic profile of the cancer. The PACT test is an in vitro diagnostic test cleared by the U.S. Food and Drug Administration (FDA) to guide clinical decision-making for patients diagnosed with malignant solid tumors. By revealing the genetic blueprint of a cancer, the test informs healthcare providers about which targeted therapies are most likely to be effective.
The Molecular Targets of the PACT Test
The PACT test analyzes 607 genes linked to the development and progression of various cancers. These genes were selected because their roles in cancer biology are well-established or because they are known targets for currently approved cancer medications.
The primary molecular targets are somatic mutations, which are genetic changes that occur only in the tumor cells and are not inherited. The test looks for single nucleotide variants (point mutations), which are single-base changes in the DNA code. It also detects small insertions and deletions (indels), which are additions or removals of small segments of DNA code.
These genetic alterations often drive the uncontrolled growth and survival of cancer cells by affecting the proteins they produce. For instance, a point mutation in a specific gene might cause a protein to be permanently “switched on,” leading to continuous cell division. Identifying these oncogenic drivers allows for the choice of a targeted drug designed to block that specific faulty protein.
To ensure it analyzes only tumor-specific changes, the PACT test compares the DNA sequence from the patient’s tumor tissue against the DNA from a matched normal specimen. This comparison distinguishes between a somatic mutation, which is acquired in the tumor, and an inherited germline variant, which is present in all the patient’s cells. The test also includes genes related to compounds currently in late-stage clinical trials, matching patients to experimental therapies when standard options are limited.
Sample Collection and Laboratory Processing
The PACT test begins with the collection of a tumor sample, typically obtained through a biopsy or surgical resection. The preferred material is formalin-fixed, paraffin-embedded (FFPE) tissue, a standard method used to preserve tissue specimens. A small amount of this preserved tumor tissue is sent to the molecular pathology laboratory for processing.
The first step is the extraction of genomic DNA from the preserved tissue. This requires sufficient material to isolate DNA, usually between 100 and 250 nanograms, for accurate sequencing. A matched normal tissue sample, often obtained from the patient’s blood, is also processed to provide a baseline DNA sequence for comparison.
The extracted DNA then undergoes library preparation, where fragments are tagged with unique molecular barcodes and prepared for sequencing. This targeted approach ensures that only the 607 genes of interest are amplified and sequenced. The prepared DNA libraries are loaded onto a high-throughput next-generation sequencing instrument, where the sequence of the DNA bases is determined.
The raw sequencing data is fed into a bioinformatics pipeline for analysis. This system converts the DNA reads into a structured report detailing the specific genetic alterations found in the tumor. An internal quality control check analyzes single nucleotide polymorphisms (SNPs) to create a genetic “fingerprint,” ensuring no sample mix-up occurred between the tumor and normal specimens.
Understanding PACT Test Results and Clinical Implications
The final PACT test result is a comprehensive molecular diagnostic report tailored for the treating oncologist. The report translates complex genetic data into clinically meaningful information that directly impacts patient care by classifying detected somatic variants based on their established clinical significance.
The variants are sorted into specific, FDA-recommended categories to streamline interpretation. The highest level of findings, Level 2, are designated as “Cancer Mutations with Evidence of Clinical Significance,” indicating a strong link to an approved therapy or prognostic information. The next tier, Level 3, classifies “Cancer Mutations with Potential Clinical Significance,” which may correspond to investigational therapies or drugs approved for a different type of cancer.
The test focuses strictly on actionability, avoiding findings that are not known to affect treatment decisions. Variants of unknown clinical significance, as well as benign or likely benign variants, are typically not included. This filtration ensures the physician receives a concise summary of genetic changes that can be directly matched with targeted therapies or immunotherapies.
The ultimate clinical implication of the PACT test is its ability to guide precision oncology by linking a patient’s tumor genetics to the best therapeutic options. For a patient with a specific mutation, the report may recommend a targeted drug that selectively inhibits the faulty protein caused by that mutation, potentially leading to a more effective response than broad chemotherapy. Furthermore, the results help identify a patient’s eligibility for specific clinical trials, offering access to experimental treatments suited to their cancer’s genetic profile.