**1. Introduction**

Over the last 40 years, several million lung cancer patients have received platinum-based regimens, and despite the clinical use of an impressive variety of targeted agents, these drugs are still one of the main therapeutic options for certain patients [1]. Platinum compounds are also the best choice in first-line immunotherapy combinations [2]. However, despite the good impact of platinum-based therapies, only a small proportion of patients have durable benefits [3]. Therefore, biomarkers to explain the resistance mechanisms to platinum compounds are urgently needed.

*KRAS* mutations have long been considered potential biomarkers to predict the outcome of platinum-based chemotherapy in NSCLC [4]. The TAILOR trial data shed light on the possibility that there was a small negative prognostic effect of *KRAS* mutations in advanced NSCLC patients treated with a platinum-based doublet when EGFR-mutant patients were excluded from the analysis [5].

Platinum adducts are repaired by different DNA repair systems. The Fanconi anemia (FA) pathway is thought to coordinate these systems, including homologous recombination (HR), nucleotide excision repair (NER), and translesion synthesis (TLS) repair [6,7]. Other DNA repair systems, such as base excision repair (BER), are involved in cisplatin-induced DNA damage, but so far, they have been assigned only a marginal role in repairing this damage [8].

Our group recently reported in a preclinical study that DNA polymerase β, an important component of the BER pathway, could be involved in platinum-based chemotherapy responses. Our results suggested a different pattern of sensitivity/resistance to cisplatin, dependent on *KRAS* mutational status [9].

The present work explores whether DNA polymerase β, alone or in combination with *KRAS* mutational status, can identify tumors with different abilities to respond to platinum compounds. This is the first study to prospectively assess the combined role of the selected biomarkers to identify patients who could benefit from platinum-based therapy.
