Emerging therapeutic agents for advanced non-small cell lung cancer

Abstract

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first inhuman or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.

The Interplay between Cancer Biology and the Endocannabinoid System—Significance for Cancer Risk, Prognosis and Response to Treatment

“…In 2018, over two million new lung cancer (LC) cases were diagnosed, and over 1.3 million people have died from LC, making this disease the most common occurring malignant disease in the world, as well as the most common cause of cancer-related deaths [59]. Although LC is a model cancer for the success of molecular targeted therapies [105,106], due to the high cost of radiologically-based nation-wide screening programs [107,108], it is most often diagnosed in advanced disease stages when the level of cancer-related pain is high [109]. An individual combination of pharmacological and non-pharmacological approaches for each patient ensures the optimal palliative care which results in higher quality of life and longer survival.…”

“…However, the burden of evidence on the efficacy of concurrent cannabis use with various cancer treatments is still not sufficiently strong to result in official recommendations of their use in this setting. The interaction between the downstream effects of approved chemo-, targeted and immunotherapy drugs for LC [106] and the metabolism of cannabinoids is complex, which calls for caution in the interpretation of data derived from uncontrolled studies. Some ECS components have shown a direct anti-cancer potential by modulating various signalling pathways (ERK, PI3K, p38 MAPK, ceramide pathways), thus inducing apoptosis and/or the inhibition of cell proliferation and epithelial-to-mesenchymal transition (EMT) [117].…”

<p>LncRNA LINC01116 Contributes to Cisplatin Resistance in Lung Adenocarcinoma</p>

“…5 Currently, platinum-based combination chemotherapy like cisplatin and carboplatin, is the standard treatment for NSCLC, which has been proved to effectively prolong the overall survival (OS). 6 However, the chemotherapy efficacy is greatly limited by the drug resistance, and a majority of the patients may experience disease progression, resulting in chemotherapy failure. 7 Despite multiple attempts to illustrate the molecular mechanisms underlying cisplatin resistance, the exact mechanisms of cisplatin resistance have not been fully demonstrated in NSCLC until now.…”

Patients with high-grade alectinib-induced skin rash: How do we desensitize these patients? A case report and review of literature

“…The anaplastic lymphoma kinase (ALK) gene rearrangement is found in 2%–7% of advanced non-small-cell lung cancer (NSCLC) patients. 1 Tyrosine kinase inhibitors (TKIs) that target this rearrangement are more effective in the management of such patients, with improved response rate and progression-free survival compared with chemotherapy. Alectinib is one of the first-line treatments for ALK-positive stage-IV lung adenocarcinoma.…”

“…Alectinib is one of the first-line treatments for ALK-positive stage-IV lung adenocarcinoma. 1 , 2 Severe (⩾Grade 3) skin rash due to the medication is rare. In the ALEX trial, 1% of patients developed Grade 3 rash, while in the J-ALEX trial, 2.9% developed Grade 3 rash.…”