Targeting the translation machinery in cancer.
Dysregulation of mRNA translation is a frequent feature of neoplasia. Many oncogenes and tumour suppressors affect the translation machinery, making aberrant translation a widespread characteristic of tumour cells, independent of the genetic make-up of the cancer. Therefore, therapeutic agents that target components of the protein synthesis apparatus hold promise as novel anticancer drugs that can overcome intra-tumour heterogeneity. In this Review, we discuss the role of translation in cancer, with a particular focus on the eIF4F (eukaryotic translation initiation factor 4F) complex, and provide an overview of recent efforts aiming to 'translate' these results to the clinic.
1] Goodman Cancer Research Centre, 1160 Pine Avenue West, Montreal, Quebec, H3A 1A3, Canada. [2] McGill University Health Centre, Division of Gastroenterology, 687 Pine Avenue West, Montreal, Quebec, H3A1A1, Canada. [3].
Mamatha
M
Bhat
1] Goodman Cancer Research Centre, 1160 Pine Avenue West, Montreal, Quebec, H3A 1A3, Canada. [2] Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada. [3].
Nathaniel
N
Robichaud
1] Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, Quebec, H3T 1E2, Canada. [2] Department of Oncology, McGill University, 546 Pine Avenue West, Montreal, Quebec, H2W 1S6, Canada. [3].
Laura
L
Hulea
1] Goodman Cancer Research Centre, 1160 Pine Avenue West, Montreal, Quebec, H3A 1A3, Canada. [2] Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada.
Nahum
N
Sonenberg
1] Goodman Cancer Research Centre, 1160 Pine Avenue West, Montreal, Quebec, H3A 1A3, Canada. [2] Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada.
Jerry
J
Pelletier
1] Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, Quebec, H3T 1E2, Canada. [2] Department of Oncology, McGill University, 546 Pine Avenue West, Montreal, Quebec, H2W 1S6, Canada.
Ivan
I
Topisirovic
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D012333:RNA, Messenger