Epidermal growth factor receptor (EGFR) is a known target in cancer therapy and 
targeting the receptor has proven to be extremely successful in treating cancers 
that are dependent on EGFR signaling. To that effect, targeted therapies to EGFR 
such as Cetuximab, Panitumumab-monoclonal antibodies and Gefitinib, 
Erlotinib-tyrosine kinase inhibitors have had success in therapeutic scenarios. 
However, the development of resistance to these drugs makes it necessary to 
combine anti- EGFR therapies with other inhibitors, so that resistance can be 
overcome by the targeting of alternate signaling pathways. On the other hand, 
components of the inflammatory pathway, within and around a tumor, provide a 
conducive environment for tumor growth by supplying numerous cytokines and 
chemokines that foster carcinogenesis. Interleukin 6 (IL-6) is one such cytokine 
that is found to be associated with inflammation-driven cancers and which also 
plays a crucial role in acquired resistance to anti-EGFR drugs. The EGFR and 
IL-6 signaling pathways crosstalk in multiple ways, through various mediators 
and downstream signaling pathways driving resistance and hence co-targeting them 
has potential for future cancer treatments. Here we provide an overview on the 
crosstalk between the EGFR and IL-6 pathways, and discuss how co-targeting these 
two pathways could be a promising combination therapy of the future.