KRAS G12 isoforms exert influence over up-front treatments: A retrospective, multicenter, Italian analysis of the impact of first-line immune checkpoint inhibitors in an NSCLC real-life population.

Background: KRAS is commonly mutated in non-small cell lung cancer (NSCLC); however, the prognostic and predictive impact of each G12 substitution has not been fully elucidated. The approval of specific G12C inhibitors has modified the idea of KRAS "undruggability", and although the first-line standard consists of immune checkpoint inhibitors (ICIs) with or without chemotherapy, as suggested at ASCO 2022, the outcome in KRAS-mutated population is still controversial.

Methods: We retrospectively described the clinical and pathological characteristics of a homogeneous G12 mutated cohort of 219 patients treated in four Italian oncologic units.

Gender Matters. Sex-related Differences in Immunotherapy Outcome in Patients with Non-small Cell Lung Cancer.

Background: Emerging evidence identified sex as a variable regulating immune system functions and modulating response to immunotherapy in cancer patients.

Objective: This retrospective study analysed sex-related differences in immunotherapy outcomes in a real-world population of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).

Methods: e retrospectively investigated clinical data of 99 patients with advanced NSCLC and treated with single-agent nivolumab and pembrolizumab at Medical Oncology Unit, Careggi University Hospital, Florence (Italy), between April 2014 to August 2019.

New options on the horizon for nononcogene addicted non-small-cell lung cancer.

The treatment of non-small-cell lung cancer (NSCLC) has historically been based on platinum doublets- and taxan-based chemotherapy in the first- and second-line therapy, respectively. Although new agents have emerged for patients with driver mutations, treatment options for nononcogene addicted NSCLC have not changed for years. However, the last 5 years have seen the approval and introduction of new biological agents, such as immune checkpoint inhibitors and antiangiogenic drugs.

Osimertinib in patients with advanced epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer: rationale, evidence and place in therapy.

The identification of epidermal growth factor receptor () mutations represented a fundamental step forward in the treatment of advanced non-small cell lung cancer (NSCLC) as they define a subset of patients who benefit from the administration of specifically designed targeted therapies. The inhibition of mutant through -tyrosine kinase inhibitors (TKIs), either reversible, first-generation gefitinib and erlotinib, or irreversible, second-generation afatinib, has dramatically improved the prognosis of patients harboring this specific genetic alteration, leading to unexpected clinical benefit. Unfortunately, virtually all patients who initially respond to treatment develop acquired resistance to -TKIs within 9-14 months.

Immune checkpoint blockade in small cell lung cancer: is there a light at the end of the tunnel?

Small cell lung cancer (SCLC) is a very aggressive disease, characterised by rapid growth, high response rates to both chemotherapy and radiotherapy and subsequent development of treatment resistance in the vast majority of patients. In the past 30 years, little progress has been made in systemic treatments and the established management paradigm of platinum-based chemotherapy has reached an efficacy plateau. Several clinical trials have investigated targeted therapies, without producing clinically significant benefits.

Targeting EGFR and ALK in NSCLC: current evidence and future perspective.

The advent of molecular therapy targeting specific driver oncogenes has dramatically changed the prognosis of a subset of NSCLC, dilating survival and improving the quality of life of patients with advanced disease. Two of the major targets for treatment with receptor TKIs are the activated mutated forms of the and the gene fusions. In advanced NSCLC patients harboring mutations or rearrangements, the use of TKIs in the first-line setting, have provided unexpected large progression-free survival and overall survival benefits, compared with cytotoxic chemotherapy.

Long noncoding RNAs: new insights into non-small cell lung cancer biology, diagnosis and therapy.

Recent advances in tiling array and high throughput analyses revealed that at least 87.3 % of the human genome is actively transcribed, though <3 % of the human genome encodes proteins. This unexpected truth suggests that most of the transcriptome is constituted by noncoding RNA.

Targeting the KRAS variant for treatment of non-small cell lung cancer: potential therapeutic applications.

Lung cancer is the leading cause of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 80% of all lung cancers. Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the deadliest cancer-related proteins and plays a pivotal role in the most aggressive and lethal human cancers, including lung adenocarcinoma where it represents one of the most frequently mutated oncogene. Although therapeutic progresses have made an impact over the last decade, median survival for patients with advanced lung cancer remains disappointing, with a 5-year worldwide survival rate of <15%.

miRNAs and resistance to EGFR-TKIs in EGFR-mutant non-small cell lung cancer: beyond 'traditional mechanisms' of resistance.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of advanced non-small cell lung cancers (NSCLCs) that harbour specific EGFR activating mutations. However, the efficacy of an EGFR-TKI is limited by the onset of acquired resistance, usually within one year, in virtually all treated patients. Moreover, a small percentage of EGFR-mutant NSCLCs do not respond to an EGFR-TKI, thus displaying primary resistance.

Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK-positive non-small cell lung cancer: Results of a multicenter analysis.

Objectives: Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI). However, the benefit of sequential treatment with a 2nd ALK-TKI in patients who fail a 1st ALK-TKI has been poorly addressed.

Materials And Methods: We collected the data of 69 advanced ALK-positive NSCLCs who were treated with one or more ALK-TKIs at three Italian institutions.

Incidence of Ct scan-detected pulmonary embolism in patients with oncogene-addicted, advanced lung adenocarcinoma.

Background: Patients with stage IIIB-IV lung adenocarcinoma are at high-risk for pulmonary embolism (PE). In these patients, EGFR and KRAS mutations as well as EML4/ALK rearrangements are recognized as "drivers" and as targets for therapy. Data on the incidence of PE in oncogene-addicted lung cancer patients are limited.