Article
Oncology
Takafumi Fukui, Motoko Tachihara, Tatsuya Nagano, Kazuyuki Kobayashi
Summary: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) has made significant progress in recent years with the development of multiple tyrosine kinase inhibitors (TKIs) targeting ALK. Clinical trials of novel ALK-TKIs, angiogenesis inhibitors, immune checkpoint inhibitors, and chemotherapy are ongoing, and tissue and liquid biopsy are being explored as methods to investigate resistance mechanisms. This manuscript aims to provide information on these recent clinical trials and propose a treatment algorithm for ALK-rearranged advanced NSCLC.
Review
Oncology
Li Wang, Wen Wang
Summary: ALK-TKIs have shown excellent clinical efficacy in treating ALK-positive NSCLC as first-line therapy, but resistance and adverse effects remain challenges. Proper management of these adverse effects is crucial in improving patient quality of life.
Review
Pharmacology & Pharmacy
Diego Kauffmann-Guerrero, Kathrin Kahnert, Rudolf M. Huber
Summary: Non-small-cell lung cancer (NSCLC) constitutes the majority of lung cancer cases, with emerging targeted therapies providing significant progress in treating a subset of patients. ALK tyrosine kinase inhibitors have greatly improved treatment options and outcomes for ALK-positive NSCLC patients.
Review
Oncology
Delphine Antoni, Helene Burckel, Georges Noel
Summary: The use of tyrosine kinase inhibitors has significantly improved outcomes for ALK-rearranged non-small cell lung cancer patients, and combining them with radiotherapy may increase effectiveness or overcome resistance. The identification of genetic alterations, such as ALK rearrangements in NSCLC patients, has led to a transformation in targeted therapies. The combination of ALK inhibitors and radiotherapy shows potential for improving treatment outcomes, although further research is needed to determine safety and efficacy.
Article
Immunology
Annkristin Heine, Stefanie Andrea Erika Held, Solveig Nora Daecke, Chrystel Flores, Peter Brossart
Summary: This study investigates the immunosuppressive effects of two different ALK inhibitors on dendritic cells. The results show that crizotinib significantly suppresses the activation, migration, and cytokine production of dendritic cells, while alectinib has lesser immunosuppressive effects.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Swati Soni, Ashu Rastogi, Kuruswamy T. Prasad, Digambar Behera, Navneet Singh
Summary: This study aimed to evaluate the incidence of thyroid dysfunction in NSCLC patients treated with EGFR and ALK inhibitors, showing that 8% of patients developed thyroid dysfunction typically within one month of treatment initiation. However, all patients were asymptomatic and none required interruption or cessation of TKI treatment.
Article
Biology
Xiaolong Tang, Lizhi Cheng, Guo Li, Yong-Ming Yan, Fengting Su, Dan-Ling Huang, Shuping Zhang, Zuojun Liu, Minxian Qian, Ji Li, Yong-Xian Cheng, Baohua Liu
Summary: The small molecule compound D6 demonstrates promising efficacy in treating EGFR-TKI resistant NSCLC by targeting the protein-protein interaction between HSP90 and T790M-EGFR, offering a potential alternative strategy to overcome drug resistance.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Simon Baldacci, Benjamin Besse, Virginie Avrillon, Bertrand Mennecier, Julien Mazieres, Pascale Dubray-Longeras, Alexis B. Cortot, Renaud Descourt, Helene Doubre, Xavier Quantin, Michael Duruisseaux, Isabelle Monnet, Denis Moro-Sibilot, Jacques Cadranel, Christelle Clement-Duchene, Sophie Cousin, Charles Ricordel, Patrick Merle, Josiane Otto, Sophie Schneider, Alexandra Langlais, Franck Morin, Virginie Westeel, Nicolas Girard
Summary: In this study, the researchers evaluated the treatment sequencing, efficacy, and safety of lorlatinib in patients with ALK+ NSCLC through the French Expanded Access Program. The results showed that lorlatinib provided significant clinical benefit and high intracerebral antitumor activity in heavily pretreated patients with ALK+ NSCLC.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Oncology
Xin-Rui Zhang, Pham-Ngoc Chien, Sun-Young Nam, Chan-Yeong Heo
Summary: Anaplastic large cell lymphoma is a rare disease with four subtypes that differ in clinical symptoms, gene changes, prognosis, and treatment.
Review
Oncology
Yunxia Tao, Yu Zhou, Le Tang, Haizhu Chen, Yu Feng, Yuankai Shi
Summary: This study conducted a meta-analysis to evaluate the toxicity profile of anaplastic lymphoma kinase (ALK) inhibitors in patients with ALK-positive non-small cell lung cancer (NSCLC). The analysis found that ALK inhibitors were associated with various adverse events, with moderately high yet manageable rates of grade >= 3 AEs. Different ALK inhibitors exhibited distinct toxicity spectrums.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Medicine, General & Internal
Shih-Lung Chen, Kai-Chieh Chan
Summary: ALCL is a rare form of non-Hodgkin's lymphoma, especially when it occurs in the external auditory canal (EAC). Diagnosis of ALCL in the EAC region can be challenging, but a combination of imaging, histopathological examination and IHC staining can confirm the presence of the disease. Treatment options include radiotherapy, chemoradiotherapy, and targeted therapies like Brentuximab vedotin for ALK-positive ALCL.
Review
Pharmacology & Pharmacy
Niels Heersche, G. D. Marijn Veerman, Mirjam de With, Sander Bins, Yehuda G. Assaraf, Anne-Marie C. Dingemans, Ron H. N. van Schaik, Ron H. J. Mathijssen, Frank G. A. Jansman
Summary: Small-molecule kinase inhibitors play a crucial role in the treatment of non-small cell lung cancer patients with genetic driver mutations. However, the treatment efficacy and drug resistance vary greatly among patients, which can be attributed to factors such as oral administration, drug interactions, and germline variations.
DRUG RESISTANCE UPDATES
(2022)
Article
Medicine, Research & Experimental
Bayan Maraqa, Maxim Al-Ashhab, Maher A. Sughayer
Summary: This study examined the prevalence of ALK rearrangement in Jordanian patients with NSCLC and compared the results of IHC and FISH for detecting ALK rearrangement. The sensitivity and specificity of ALK immunostaining compared with FISH were calculated. ALK rearrangement was significantly associated with age, gender, and smoking history.
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
(2022)
Article
Oncology
Petros Christopoulos, Farastuk Bozorgmehr, Lena Bruckner, Inn Chung, Johannes Krisam, Marc A. Schneider, Albrecht Stenzinger, Regina Eickhoff, Daniel W. Mueller, Michael Thomas
Summary: The study aims to optimize the management of ALK(+) NSCLC by analyzing the efficacy of second-generation ALK inhibitors and conducting deep longitudinal phenotyping analysis. Patients will be randomized into two treatment arms, with biomarker analysis conducted to investigate baseline tumor properties and analyze the development of acquired drug resistance. Fast-track molecular tumor and ctDNA profiling will also be available for therapeutic decisions at the time of disease progression.
Review
Medicine, General & Internal
L. B. Cameron, N. Hitchen, E. Chandran, T. Morris, R. Manser, B. J. Solomon, V Jordan
Summary: This study evaluated the safety and efficacy of ALK inhibitors as monotherapy for advanced ALK-rearranged NSCLC. The results showed that ALK inhibitors are effective in improving progression-free survival, overall survival, and overall response rate, with minimal adverse events compared to chemotherapy. Next-generation ALK inhibitors are more effective and safe than first-generation ALK inhibitors. However, further research is needed to compare different next-generation ALK inhibitors.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2022)