“If you have lung cancer, in addition to knowing its histology, you should ask your oncologist if the tumor is positive for alteration regarding EGFR, ALK, ROS1, PD-L1 or BRAF genes to receive optimal care.”
– Dr. Vanesa Gregorc –

Genomic test for personalized therapy

Genomic Test Lung Cacner

Thanks to new DNA sequencing techniques, it is possible to sequence whole genomes and/or transcriptomes in a short time. It is now clear that lung cancer is a very heterogenous disease from a molecular point of view, with significant differences based on the smoking habit, both in terms of quantity and quality. In fact, it has been observed that smokers have a higher frequency of gene mutations, which are different from those seen in non-smoking patients.

For non-small cell lung tumors in particular, the discovery of some genetic alterations allowed the development of targeted therapeutic strategies.

To assess the possibility of using personalized medicine (or precision medicine) on a lung cancer patient, it may be useful to use genomic tests that would recognize clinically relevant DNA alterations.

FoundationOne®CDx (by Foundation Medicine®) is a certified genomic test for solid tumors that allows for an extensive assessment of the tumoral profile, using the Next Generation Sequencing (NGS) technique based on Hybrid Capture.

Starting from a small tissue sample obtained by a biopsy, FoundationOne®CDx simultaneously analyzes up to 324 tumor-related genes to detect:

  • The four main classes of genomic alterations (base substitutions, insertions and deletions, copy number variations, rearrangements),
  • Biomarkers of microsatellite instability (MSI) and tumor mutational burden (TMB), which helps predict the patient’s response to immunotherapy.

In addition to tracing a tumor profile, the Foundation Medicine® diagnostic service reports the most suitable therapies for the alterations detected by the test, indicating not only the drugs available on the market, but also those under development or any clinical trials in which the patient could be recruited. All this information supports the specialist in their evaluation of targeted therapies for each tumor and offers the patient more treatment opportunities.

The goal of Alliance Against Cancer (Alleanza Contro il Cancro or ACC), in collaboration with the Ministry of Health, is to apply NGS in all new cases of patients with non-small cell lung cancer in the locally advanced or metastatic stage from the 20 institutes affiliated with ACC. Currently, the FoundationOne®CDx test may also be performed privately.


In current clinical practice, the alterations for which it is possible to use one of these molecular or biological targeted therapies are the EGFR gene mutations (see Therapies for patients with EGFR mutations) and the fusion alteration involving ALK gene (see Therapies for ALK positive patients).

RET and ROS1

Rarer alterations include fusions involving the genes REarranged during Transfection (RET) and V-ROS Avian UR2 Sarcoma Virus Oncogene Homolog 1 (ROS1). ROS1-positive patients can benefit from the same category of drugs used against ALK positive tumors.


Other gene mutations present in non-small cell lung cancer are ‘orphans’ of targeted therapies. An example of this is the case of Kirsten rat sarcoma viral oncogene homolog (KRAS).

All the alterations discussed so far are typical of a particular histotype of non-small cell tumors, adenocarcinomas and are more frequent in non-smoking patients, except mutations in KRAS.


NSCLC by histology

As for the squamous cell histotype (typical tumor of smokers), for which, at present, there are no targeted treatments against the specific gene alterations that characterize it, the most frequently changed genes are P53, PIK3CA, PTEN, FGFR1, DDR2.


The introduction of immunotherapeutic drugs into clinical practice also emphasized the importance of characterizing a tumor’s PD-L1 status. The registration of pembrolizumab as a first-line treatment for patients with a PD-L1 expression of >50% made it fundamental to evaluate this marker at time of diagnosis due to the important therapeutic implications this information may provide.

Mutational load

The molecular classification of lung cancer has made it possible to define different categories of tumors based on the number of genetic alterations present, which is also known as the tumor’s ‘mutational burden’.

The FoundationOne®CDx genomic test also detects the tumor mutational burden (TMB), providing more possibilities to better identify patients who can benefit from immunotherapy.