A definitive study randomizing patients with ALK-mutant lung cancer to crizotinib (also known as PF-02341066 or 1066) versus standard therapy has recently completed enrollment.Taken together, these data describe a trajectory of research progress from basic discovery science to real-world implementation that should serve as a model for future integration of preclinical and clinical therapeutic research.
Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).
The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients.
Here, we report a novel <i>VKORC1L1-ALK</i> fusion and an ALKT1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years.
Although there is a possibility that the left lung cancer is de novo one with multiple metastases, detection of the same fusion gene of the very rare EML4-ALK variant 1 in both tumors suggests that the left cancer is a recurrence of the right lung cancer after an interval of 15 years.
The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas.<b>Experimental Design:</b> Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC.<b>Results:</b> The use of targeted therapies in patients with <i>EGFR, ERBB2,</i> or <i>BRAF</i> p.V600E mutations, <i>ALK, ROS1</i>, or <i>RET</i> rearrangements, or <i>MET</i> amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver.
In recent years molecular subtyping has become an important tool for accurate diagnosis of many cancers; for example, the detection of ALK rearrangements in lymphoma and lung cancer helps clinicians provide more precise diagnosis and treatment.
Mutations in epidermal growth factor receptor (<i>EGFR</i>), and rearrangements of anaplastic lymphoma kinase (<i>ALK</i>) are targetable in lung cancer, while <i>BRAF</i> mutations have been successfully targeted in metastatic melanoma.
The discovery of the EML4-ALK fusion kinase in 2007 was a breakthrough for this situation, and kinase fusion genes now form a group of relevant targetable oncogenes in lung cancer.
Our data argue against PDGFRB activation in association with ALK gene aberrations in metastatic NSCLC and thus seem to imply differential pathobiological roles of ALK alterations in lung cancer and lymphoma, possibly depending on different fusion partner genes.
Clinical and computed tomography characteristics of non-small cell lung cancer with ALK gene rearrangement: Comparison with EGFR mutation and ALK/EGFR-negative lung cancer.
These data suggest that overexpression of EGFR ligands such as AREG can cause resistance to crizotinib, and that inhibition of EGFR signaling may be a promising strategy to overcome crizotinib resistance in EML4-ALKlung cancer.
The recent discovery of ALK translocations in adult lung cancer patients (non-small cell lung cancer) has accelerated the development of inhibitors of ALK tyrosine kinase as therapeutic agents.
These observations indicate that signals from oncogenic drivers (EGFR signaling in EGFR -mutant lung cancer and ALK signaling in EML4-ALKlung cancer) and ligand-triggered bypass signals (HGF-Met and EGFR ligands-EGFR, respectively) must be simultaneously blocked to avoid the resistance.
We present the PET/CT findings of extensive disseminated genital herpes simplex virus infection in a 29-year-old woman known with disseminated anaplastic lymphoma kinase-mutated nonsmall lung cancer.
However, emerging genomic data from the Cancer Genome Atlas (TCGA, USA) are now revealing common ALK point mutations (~3.06%) in various cancer types other than lung cancer.
EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers.