[Combi-molecules: a global approach towards better chemoselectivity and chemosensitivity].
It is now known that tumour cells possess many signaling pathways to repair damage inflicted by alkylating agents. However, most of these cytotoxic agents only target DNA and this does not suffice to induce sustained antiproliferative activity. Furthermore, the efficacy of antitumour alkylating agents is hampered by a lack of selectivity for tumour tissues. To circumvent these problems, we recently designed a novel strategy termed combi-targeting that sought to synthesize compounds capable of not only damaging DNA, but also blocking signaling associated with aggressive proliferation. The first prototypes described herein can block signaling associated with the epidermal growth factor receptor (EGFR) and significantly damage DNA. In addition to their binary EGFR/DNA targeting properties, we demonstrated that their effects are selective for cells to which EGFR has conferred a proliferative advantage. These novel agents with mixed targeting properties are termed "combi-molecules".
Matheson
Stéphanie
S
Cancer Drug Research Laboratory, Division of Medical Oncology/Department of Medicine, Royal Victoria Hospital/McGill University Health Center, 687 Pine Avenue West Rm M719 H3A 1A1, Montréal, Canada.
Qiu
Qiyu
Q
Brahimi
Fouad
F
Dudouit
Fabienne
F
Banerjee
Ranjita
R
Rachid
Zakaria
Z
Jean-Claude
Bertrand J
BJ
D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000627:therapeutic use; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D011799:Quinazolines / Q000138:chemical synthesis* / Q000627:therapeutic use
D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; C471268:FD137 nitrosourea; D009607:Nitrosourea Compounds; D011799:Quinazolines; C421705:SMA-41; D066246:ErbB Receptors