This first draft of my abstract is the result of careful and meticulous revisions to quite a few sentences to reduce the word count to fewer than 200 words. Who knew how tough it would be to fit so many of the ideas swirling around my brain into less than 200 words? Words fly when you’re having fun.
ABSTRACT – Both ABL and DDR kinases appear particularly hyperactive in the context of chemoresistance, in which cancer cells become resistant to chemotherapy. Furthermore, preliminary data suggest that receptor tyrosine kinases, DDR1 and DDR2, are ABL kinase targets. Thus, the hypothesis that DDR and ABL kinases form a feedback loop and that hyperactivation of the ABL-DDR network occurs during therapy resistance was tested. Due to the suggestion that DDR kinases are implicated in subsets of breast and lung cancers, DDR1/2 expression in these cancers was evaluated. It was demonstrated that increased ABL2 activity using the constitutively active form of ABL2 (ABL2-PP) in lung cancer cells induces phosphorylation of DDR1, whereas treatment with the ABL kinase allosteric inhibitor, GNF5, and the ABL and DDR kinase inhibitor, Nilotinib, decreases DDR1 phosphorylation without decreasing total DDR1 amounts. These data suggest that DDR kinases are downstream targets of ABL kinases, which supports the idea that DDR and ABL kinases constitute a novel signaling axis. If hyperactivation of the ABL-DDR network is indeed important during therapy resistance, there is potential that inhibition of the multifunctional ABL kinases through targeted therapy will resensitize cancer cells to the treatment to which they had been resistant before.
To be continued… as I add the results of the experiments I plan to perform next week, fresh from the oven!
Note: “Fresh from the oven” is solely meant to convey the idea that new and not yet acquired data are still to be incorporated into my abstract. I do not actually carry out my experiments in an oven. 😉
Update: For those of you who are interested, here is the final draft of my abstract, in all of its glory:
Novel signaling axis between ABL and DDR kinases in chemoresistance and metastasis: promise for targeted therapy in breast and lung cancers?
In the context of metastasis and chemoresistance in lung and breast cancer cells, the ABL family of tyrosine kinases and the receptor tyrosine kinases, DDR1 and DDR2, have been revealed to be hyperactive. My preliminary data suggest that the DDR kinases are ABL kinase targets. We hypothesize that DDR and ABL kinases form a feedback loop and that hyperactivation of the ABL-DDR network occurs during therapy resistance in subsets of breast and lung cancers. My data demonstrate that increased ABL2 activity using the constitutively active form of ABL2 (ABL2-PP) in lung cancer cells induces phosphorylation of DDR1; however, treatment with the ABL kinase allosteric inhibitor, GNF5, and the ABL and DDR kinase inhibitor, Nilotinib, decreases DDR1 phosphorylation without decreasing total DDR1 expression. These results suggest a novel ABL-DDR signaling axis, and preliminary data suggest that hyperactivation of this pathway may be important during metastasis and therapy resistance. Importantly, we demonstrated that pharmacological inhibition of the ABL kinases resensitizes therapy-refractory tumor cells to standard-of-care chemotherapy.