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New options in the management of intractable ALK(+) metastatic non-small-cell lung cancer
Amy M Weise1, Shirish Gadgeel1
1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Abstract:
Non-small-cell lung cancer (NSCLC) is a heterogeneous disease and a challenging malignancy to treat, as many patients have advanced disease at the time of diagnosis. Recent advances have led to the identification of molecularly defined subtypes of NSCLC, namely for patients with adenocarcinoma histology. The most recently identified molecular target is the anaplastic lymphoma kinase (ALK) gene rearrangement, and patient responses to the ALK inhibitor crizotinib have led to its approval in this selected patient population. Like other tyrosine kinase inhibitors, resistance to crizotinib ultimately develops by various mechanisms requiring alternative therapeutic options. This review article discusses the management of patients with the ALK gene rearrangement, mechanisms of crizotinib resistance, and future potential therapeutic options.
Insights
Anaplastic lymphoma kinase (ALK) gene rearrangement targets non-small-cell lung cancer (NSCLC). Crizotinib is approved for ALK-positive NSCLC, but resistance necessitates alternative treatments and further research.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Non-small-cell lung cancer (NSCLC) presents significant treatment challenges, often diagnosed at advanced stages.
- Molecularly defined subtypes, particularly in adenocarcinoma histology, offer targeted therapeutic strategies.
- Anaplastic lymphoma kinase (ALK) gene rearrangement is a key molecular target in NSCLC.
Purpose of the Study:
- To review the management of NSCLC patients with ALK gene rearrangement.
- To discuss mechanisms of resistance to the ALK inhibitor crizotinib.
- To explore future therapeutic options for ALK-rearranged NSCLC.
Main Methods:
- Literature review of studies on ALK-rearranged NSCLC.
- Analysis of crizotinib efficacy and resistance mechanisms.
- Synthesis of current and emerging treatment strategies.
Main Results:
- Crizotinib is an effective ALK inhibitor for a subset of NSCLC patients.
- Various mechanisms contribute to the development of crizotinib resistance.
- Alternative therapeutic strategies are crucial for managing resistance.
Conclusions:
- ALK rearrangement is a critical determinant for targeted therapy in NSCLC.
- Understanding crizotinib resistance is essential for optimizing patient care.
- Continued research into novel therapies is vital for improving outcomes in ALK-positive NSCLC.
