The role of the ALK receptor in cancer biology

This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, including point mutations, deletions and rearrangements. A wide variety of ALK fusions, in which the kinase domain of ALK and the amino-terminal portion of various protein partners are fused, occur in cancer, with echinoderm microtubule-associated protein-like 4 (EML4)-ALK being the most prevalent in non-small-cell lung cancer (NSCLC). Different ALK fusion proteins can mediate different signalling outputs, depending on properties such as subcellular localisation and protein stability. The ALK fusions found in tumours lack spatial and temporal regulation, which can also affect dimerisation and substrate specificity. Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development. These ALK TKIs bind slightly differently within the ATP-binding pocket of the ALK kinase domain and are associated with the emergence of different resistance mutation patterns during therapy. This emphasises the need to tailor the sequence of ALK TKIs according to the ALK signature of each patient. Understanding the role of ALK in tumour biology is key to further optimising therapeutic strategies for ALK-positive disease. READ ARTICLE

Annals of Oncology DOI: 10.1093/annonc/mdw301

Authors: B. Hallberg, R.H. Palmer

Review PaperKirk SmithSeptember 1, 2016EML4-ALK, NSCLC, TKI, cancer biology, anaplastic lymphoma kinase (ALK)

Applications of the CRISPR–Cas9 system in cancer biology

The prokaryotic type II CRISPR–Cas9 (clustered regularly interspaced short palindromic repeats–CRISPR-associated 9) system is rapidly revolutionizing the field of genetic engineering, allowing researchers to alter the genomes of a large range of organisms with relative ease. Experimental approaches based on this versatile technology have the potential to transform the field of cancer genetics. Here, we review current approaches for functional studies of cancer genes that are based on CRISPR–Cas, with emphasis on their applicability for the development of next-generation models of human cancer. READ ARTICLE

Nature Reviews Cancer DOI: 10.1038/nrc3950

Authors: Francisco J. Sánchez-Rivera, Tyler Jacks

Review PaperKirk SmithJune 4, 2015CRISPR-Cas 9, cancer biology