1. Overview
Foundation One CDx (F1CDx) is a comprehensive genomic profiling (CGP) test designed to analyze solid tumors using next-generation sequencing (NGS) technology. It is an FDA-approved in vitro diagnostic assay that evaluates genomic alterations across 324 cancer-related genes.
The test helps determine whether a patient’s tumor harbors specific gene mutations or biomarkers that can be targeted by approved therapies. By identifying actionable genomic alterations, F1CDx supports precision oncology and personalized cancer treatment.
The assay detects all four major classes of genomic alterations, including single-nucleotide variants (SNVs), insertions and deletions (indels), copy number alterations (CNAs), and selected gene rearrangements or fusions. It also evaluates key genomic signatures such as microsatellite instability (MSI) and tumor mutational burden (TMB).
2. Symptoms
The F1CDx test itself does not address symptoms directly, as it is a diagnostic genomic assay. Clinical symptoms are related to the underlying malignancy being evaluated, such as lung, breast, colorectal, melanoma, ovarian, prostate, or other advanced solid tumors.
Patients undergoing F1CDx testing typically present with advanced or metastatic cancers where standard therapies may be ineffective or where molecular profiling is required to guide targeted or immunotherapy decisions.
3. Causes
The need for Foundation One CDx testing arises from the presence of genetic alterations within tumor cells that drive cancer development and progression. These alterations may include activating mutations, gene amplifications, deletions, or fusions that result in abnormal signaling pathways.
Cancer cells release fragmented circulating tumor DNA (ctDNA) into the bloodstream, which can be detected through liquid biopsy. Alternatively, genomic DNA can be isolated from formalin-fixed paraffin-embedded (FFPE) tumor tissue. The identification of these molecular changes enables clinicians to match patients with targeted therapies most likely to be effective.
4. Risk Factors
Foundation One CDx testing is particularly relevant for patients with advanced or treatment-resistant cancers. Risk factors prompting testing include disease progression despite standard therapy, unclear primary tumor origin, aggressive tumor behavior, or eligibility assessment for targeted therapy or immunotherapy.
The test is indicated across multiple cancer types, including non-small cell lung cancer, breast cancer, melanoma, colorectal cancer, cholangiocarcinoma, ovarian cancer, prostate cancer, and pan-tumor indications such as MSI-high, TMB-high, or NTRK fusion–positive tumors.
Patients with tumors harboring high TMB, MSI-H status, homologous recombination repair (HRR) gene mutations, or FDA-approved companion diagnostic markers are at increased likelihood of benefiting from immunotherapy or targeted agents.
5. Prevention and Clinical Management
Foundation One CDx plays a central role in guiding clinical management rather than prevention. It informs treatment selection, prognostic assessment, and therapeutic decision-making.
Blood-based liquid biopsy requires plasma samples, as serum clotting releases genomic DNA from white blood cells that can interfere with results. Blood is collected in EDTA, citrate, or heparin tubes, and plasma is separated immediately, frozen, and transported without thawing.
The assay uses targeted NGS with a hybrid-capture approach and a robust bioinformatics pipeline to analyze genomic alterations. Results provide clinically actionable insights, including eligibility for FDA-approved targeted therapies, immunotherapies, and clinical trial enrollment.
Clinically, detection of specific mutations such as EGFR, ALK, BRAF, MET, ROS1, ERBB2 (HER2), KRAS, NRAS, BRCA1/2, and NTRK fusions directly influences treatment decisions. High TMB or MSI-H status predicts a favorable response to immune checkpoint inhibitors, while HRR gene mutations guide the use of PARP inhibitors.
The test also helps avoid ineffective therapies by identifying wild-type status where targeted drugs would not be beneficial, thereby minimizing toxicity and cost. In complex or ambiguous cases, genomic profiling assists in refining diagnosis, predicting disease behavior, and improving prognostic accuracy.
Overall, Foundation One CDx enables precision oncology by matching patients to the most appropriate therapy, expanding treatment options, improving clinical outcomes, and supporting personalized cancer care.
