Interestingly, certain stromal components may have beneficial effects as a bright side such as tumor suppression, immune clearance, tissue repair (Ozdemir et al., 2014; Rhim et al., 2014), and particularly, chemosensitizing, for example, suppression of the secretion phenotype through NF-κB inhibition promoted resistance to chemotherapy in a mouse lymphoma model (Chien et al., 2011).
Interestingly, such a combination has recently shown efficacy in a mouse lymphoma model [ 66].
It has demonstrated single-agent activity against certain human cancers transplanted into immunocompromised mice and induces remission in the Eμ-myc mouse lymphoma model when combined with doxorubicin.
Thus, we tested the therapeutic efficacy in an EG7 mouse lymphoma model (EL4 cells expressing OVA as a surrogate tumour antigen).
For example, induction of Myc in a transgenic mouse lymphoma model stimulated surrounding macrophages to secrete TGFβ, which resulted in induction of cellular senescence [ 54].
Similar results have been reported in which disruption of the NF-κB-mediated SASP leads to chemo-resistance in a mouse lymphoma model (Chien et al, 2011; Jing et al, 2011).
Specifically, in a mouse lymphoma model, Schmitt et al. [ 96, 97] showed that knockout of either p16 INK4a or p19 Arf in MEFs leads to resistance to the alkylating agent cyclophosphamide.
Thus, Schmitt and colleagues [ 11] confirmed senescence activated by the concerted action of the p16/retinoblastoma and p53 pathways to cause tumour regression in response to cyclophosphamide treatment in a mouse lymphoma model.
In addition, inhibition of NF-κB-induced SASP can bypass senescence and contribute to drug resistance in a mouse lymphoma model (Chien et al, 2011; Jing et al, 2011).
As loss of Caspase-2 leads to an acceleration of tumor onset in the Eμ-Myc mouse lymphoma model, whereas loss of Pidd1 actually delays onset of this disease, we set out to interrogate the role of Raidd in cancer in more detail.
