Targeted therapy for localized non-small-cell lung cancer: a review

Zhan

et al. 2019

CMAR

PurposeRisk stratification of patients with non-small cell lung cancer (NSCLC) is crucial to select the appropriate treatments, but available models for patients with complete resection are unsatisfactory. The purpose of this study was to determine a prediction model based on clinical information, routine physical and blood tests, and molecular markers.Patients and MethodsThis was a retrospective cohort study of patients who underwent surgical resection for lung cancer between 2009 to 2013. Potential prognostic factors were used to build a full prediction model based on a multivariable Cox regression analysis. A nomogram was constructed. The risk stratification cutoffs for clinical use were determined based on the model.ResultsA total of 368 NSCLC patients with R0 resection were included. The final multivariable model indicated that low diffusing capacity of the lung for carbon monoxide (HR=1.66, 95% CI: 1.18–2.34), high platelet-to-lymphocyte ratio (HR=1.42, 95% CI: 1.04–1.95), histology type of squamous cell carcinoma and others (squamous cell carcinoma vs adenocarcinoma, HR=1.40, 95% CI: 1.01–1.96; others vs adenocarcinoma, HR=2.36, 95% CI: 1.15–4.84; P trend=0.001), N>0 status (HR=1.96, 95% CI: 1.42–2.70), high serum carcinoembryonic antigen levels (HR=1.61, 95% CI: 1.13–2.27), and postoperative chemotherapy (HR=0.53, 95% CI: 0.33–0.87) were independently associated with poor OS. The patients were classified into four risk groups according to the nomogram, and the OS was different among the four groups (P<0.05).ConclusionA nomogram was successfully constructed based on a multivariable analysis, and the nomogram can discriminate the OS of patients with NSCLC based on risk categories, but external validation is still necessary.

Section: Discussionmentioning

confidence: 99%

<p>Prediction of Overall Survival of Patients with Completely Resected Non-Small Cell Lung Cancer: Analyses of Preoperative Spirometry, Preoperative Blood Tests, and Other Clinicopathological Data</p>

Zhan

et al. 2019

CMAR

Genomics, Proteomics &Amp; Bioinformatics

“…So far, mutations of EGFR and translocations of the oncogenes encoding echinoderm microtubule-associated protein-like 4 ( EML4 ) -ALK had been identified as the most common ones [159] . Potent targeted agents against any of the identified specific genomic alterations would definitely improve the outcome of NSCLC cancer treatment [160] , [161] . Investigation of anti- ALK crizotinib (Xalkori), which targets EML4-ALK translocation, in patients with NSCLC showed promising results.…”

Section: Crizotinib Targeting Eml4-alkmentioning

confidence: 99%

Exploitation of Gene Expression and Cancer Biomarkers in Paving the Path to Era of Personalized Medicine

Kamel

Al-Amodi

2017

Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mechanisms underlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment. Cancer therapy begins to shift steadily from the traditional approach of “one regimen for all patients” to a more individualized approach, through which each patient will be treated specifically according to their specific genetic defects. Personalized medicine accordingly requires identification of indicators or markers that guide in the decision making of such therapy to the chosen patients for more effective therapy. Cancer biomarkers are frequently used in clinical practice for diagnosis and prognosis, as well as identification of responsive patients and prediction of treatment response of cancer patient. The rapid breakthrough and development of microarray and sequencing technologies is probably the main tool for paving the way toward “individualized biomarker-driven cancer therapy” or “personalized medicine”. In this review, we aim to provide an updated knowledge and overview of the current landscape of cancer biomarkers and their role in personalized medicine, emphasizing the impact of genomics on the implementation of new potential targeted therapies and development of novel cancer biomarkers in improving the outcome of cancer therapy.

“…It is a huge challenge for treatment, with a 5-year survival rate less than 18% 3, 4. Although there are multiple therapy strategies in treating lung cancer patients, such as surgery, chemotherapy, radiotherapy, molecular targeting treatment and immunotherapy 5-9, platinum-based chemotherapy is still the widely used first-line therapeutic regimen currently 10. However, the dose related toxicity and drug resistance are the main obstacles limiting the therapeutic efficiency of platinum-based chemotherapy, which are vary greatly among individuals 11, 12.…”

Section: Introductionmentioning

confidence: 99%

A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer

et al. 2019

Adenylate cyclase 1 (ADCY1 or AC1) is a member of ADCY superfamily and was primarily found to be expressed in the brain. ADCY1 is responsible for catalyzing ATP to cyclic AMP (cAMP). As a secondary messenger, cAMP can regulate plenty of cellular activities. cAMP can perform its regulation in cellular transport through the binding to cAMP dependent protein kinases (PKAs), cAMP-activated guanine exchange factors (EPACs) and cyclic nucleotide-gated channels functioning in transduction of sensory signals (CNGs). Lung cancer is one of the leading factors of cancer-related death worldwide. Platinum-based chemotherapy is the first-line treatment for advanced lung cancer patients. In addition, surgical treatment, radiation treatment, and molecular targeted therapy are also therapeutic options for lung cancer patients in clinical settings. However, drug resistance and toxicity are the major obstacles that affect chemotherapy outcome and prognosis of lung cancer patients. And the therapeutic efficiency and adverse effects are varying with each individual. In recent years, investigations based on genetic sequencing have revealed the emerging role of ADCY1 mutations in affecting drug efficiency in various cancers such as lung cancer, esophageal cancer and colorectal cancer. The potential function of ADCY1 in chemotherapy resistance is of great importance to be noticed and investigated.