CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(01): 067-070
DOI: 10.1055/s-0041-1729728
Trainees’ Corner

ALK Inhibitors in Nonsmall Cell Lung Cancer

Nitish Garg
1   Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India
Rushabh Kothari
2   Cancure Cancer Center, Narayana Multispeciality Hospital, Ahmedabad, Gujarat, India
› Author Affiliations

The management of advanced nonsmall cell lung cancer (NSCLC) has gone a definitive change over time with the discovery of small-molecule inhibitors. In 2004, the first initial description of actionable mutation of epidermal growth factor receptor (EGFR) was provided, and since then, almost 10 actionable mutations have been identified.[1] These include EGFR, anaplastic lymphoma kinase (ALK), ROS, MET, rearranged during transfection (RET), Kirsten rat sarcoma viral oncogene (KRAS), raf murine sarcoma virus oncogene homolog B (BRAF), and many others. After the development of the drugs against these receptors, these were approved by US Food and Drug Administration (FDA) for used against NSCLC with the receptor mutations.

The most common receptor tyrosine kinase mutations in adenocarcinoma lung are as follows:[2]

  1. KRAS mutation in 25% of cases of NSCLC

  2. EGFR mutation—10 to 30%

  3. MET amplification or MET exon 14 mutation—5%

  4. ALK mutation—3 to 7% cases

  5. BRAF mutations—2 to 4%

  6. Rest others: RET rearrangements, MEK1 mutation, FGFR1 amplification, Her2 mutation, ROS1 rearrangements, and NRAS mutation occur in 1% each

  7. The majority are still unknown—40%.

The drugs are very effective for patients with actionable mutant NSCLC with the response rates of 60 to 85% in the first-line setting. The main barrier is the development of resistance after a few months of treatment, which limits the duration of response to ~1 to 2 years for most of the drugs.[3]

Publication History

Article published online:
28 May 2021

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