[citation needed] Normally, the Wnt signaling pathway leads to stabilization of β-catenin through inactivation of a protein complex containing the tumor suppressors APC and Axin.
De-regulation of the autocrine Wnt signaling pathway via mutations in APC and Axin have been linked to activation of various types of human cancer.
[3] Interleukin 6 (acronym: IL-6) is a cytokine that is important for many aspects of cellular biology including immune responses, cell survival, apoptosis, as well as proliferation.
Moreover, it was shown that tumor progression selects for cells that are VEGF-dependent, challenging the belief that VEGF's role in cancer is limited to angiogenesis.
One study showed that autocrine PDGFR signaling plays an essential role in epithelial-mesenchymal transition (EMT) maintenance in vitro, which is known to correlate well with metastasis in vivo.
[6] HER2 kinase inhibitors, such as lapatinib, have also demonstrated clinical efficacy in HER2 overexpressing breast cancers by disrupting a neuregulin-1 (NRG1)-mediated autocrine loop.
[13] Recent studies have reported the ability of drug-resistant cancer cells to acquire mitogenic signals from previously neglected autocrine loops, causing tumor recurrence.
For example, despite widespread expression of epidermal growth factor receptors (EGFRs) and EGF family ligands in non-small-cell lung cancer (NSCLC), EGFR-specific tyrosine kinase inhibitors such as gefitinib have shown limited therapeutic success.
This resistance is proposed to be because autocrine growth signaling pathways distinct from EGFR are active in NSCLC cells.
Gene expression profiling revealed the prevalence of specific fibroblast growth factors (FGFs) and FGF receptors in NSCLC cell lines, and found that FGF2, FGF9 and their receptors encompass a growth factor autocrine loop that is active in a subset of gefitinib-resistant NSCLC cell lines.
In a recent study, one group showed that STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase cleavage.