New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1)

  title={New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1)},
  author={Alessandro Russo and Ana Rita Lopes and Michael G. McCusker and Sandra Garrigues and Giuseppina R. R. Ricciardi and Katherine E. Arensmeyer and Katherine A. Scilla and Ranee Mehra and Christian D. Rolfo},
  journal={Current Oncology Reports},
Purpose of Review Over the last two decades, the identification of targetable oncogene drivers has revolutionized the therapeutic landscape of non-small cell lung cancer (NSCLC). The extraordinary progresses made in molecular biology prompted the identification of several rare molecularly defined subgroups. In this review, we will focus on the novel and emerging actionable oncogenic drivers in NSCLC. Recent Findings Recently, novel oncogene drivers emerged as promising therapeutic targets… 

Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer

The molecular alterations with a potential clinical impact in NSCLC are reviewed, including amplifications or mutations of the mesenchymal–epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, and the current status of targeted agents under investigation for such alterations are summarized.

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

A comprehensive review of the emerging molecular targets in NSCLC and their applications in the advanced setting is provided.

Targeting molecular alterations in non-small-cell lung cancer: what's next?

This review has incorporated the development around MET, KRAS and NTRK in the diagnosis of NSCLC given the therapeutic potential that they represent, as well as the drugs approved for these indications.

Immunotherapy in Lung Cancer: Are the Promises of Long-Term Benefit Finally Met?

The quest for a reliable predictive biomarker is still ongoing to overcome the limits of currently approved tests for patients' selection, and the current status and progress of anti-PD-1/PD-L1 agents in lung cancer treatment is summarized.

BRAF as a positive predictive biomarker: Focus on lung cancer and melanoma patients.

Current Targeted Therapies for the Fight against Non-Small Cell Lung Cancer

This review summarizes recent developments and findings related to the generation of novel targeted therapies recently or currently being developed to tackle hurdles that prior therapies were not able to overcome.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2) and the lack of response in the ALK group was notable.



Central nervous system involvement in ALK-rearranged NSCLC: promising strategies to overcome crizotinib resistance

Evaluating the strengths and weaknesses of the therapeutic strategies developed to date in this specific subgroup of NSCLCs with a look towards the future and the results of ongoing comparative head-to-head trials with novel-generation ALK inhibitors will provide the definitive conclusions on the optimal treatment sequence.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry

In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2) and the lack of response in the ALK group was notable.

A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing.

It is demonstrated that a subset of NSCLCs could be caused by a fusion of KIF5B and RET, and suggested the chimeric oncogene as a promising molecular target for the personalized diagnosis and treatment of lung cancer.

Immunophenotype and Response to Immunotherapy of RET-Rearranged Lung Cancers

Although increasing levels of programmed death-ligand 1 expression and high tumor mutational burden have been associated with benefit from immune checkpoint blockade, the immunophenotype of RET-rearranged lung cancers and the role of PD-L1 and TMB status in relation to benefit with immunotherapy remain poorly described.

Targeting MET in Lung Cancer: Will Expectations Finally Be MET?

  • A. DrilonF. CappuzzoS. OuR. Camidge
  • Biology, Medicine
    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • 2017

The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer

Among the several NTRK-inhibitors, entrectinib and LOXO-101 are those in more advanced stage of clinical development and have shown encouraging activity along with a tolerable safety profile in patients with different solid tumors harboring N TRK-fusions, emerging as new promising therapeutic options for molecularly selected patients with advanced Trk-driven lung cancers.

Dramatic Response to Crizotinib in a Patient with Lung Cancer Positive for an HLA-DRB1-MET Gene Fusion.

The first case of a MET fusion in lung cancer identified and treated during course of clinical care is reported, and the dramatic response of the patient’s tumor to crizotinib treatment is reported.

Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort.

The results should help to define the best therapeutic strategy for these patients and to orient future clinical trials, as well as show the chemosensitivity of HER2-driven NSCLC, and the potential interest of Her2-targeted agents.

PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers

  • J. SabariG. Leonardi A. Drilon
  • Medicine, Biology
    Annals of oncology : official journal of the European Society for Medical Oncology
  • 2018
A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs and Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.

Analysis of Cell-Free DNA from 32,989 Advanced Cancers Reveals Novel Co-occurring Activating RET Alterations and Oncogenic Signaling Pathway Aberrations

In the largest cancer cohort with somatic activating RET alterations, this study finds that KIF5B-RET fusions are highly specific for NSCLC and describes novel co-occurrences of oncogenic signaling pathway aberrations.