rely , I've no idea !
but i think that : small molecule tyrosine kinase inhibitors are not synergistic with chemotherapy, while monoclonal antibodies can be synergistic with chemotherapy in lung cancer.
hint :
EGFR inhibitor ( cetuximab )
tyrosine kinase inhibitors (Erlotinib).
Acquired adaptive resistance to conventional anti-tumor drugs is due to the alternative signal activation such as EGFRvIII (glioma), mTOR (renal cell carcinoma), and amplificative EGFR (head and neck squamous cell cancer). The dual blockage with two different molecule/ signal inhibitory agents such as TKI inhibitor scetuximab or imatinib and VEGFR antagonists are currently common.
Both small molecule inhibitors and mAb are used in combination with platinum-based chemotherapy in lung cancer treatment. However, majority of patients are known to develop resistance to Erlotinib. Thus mAb such as cetuximab are preferred over small molecule inhibitors.
most biologics (including cetuximab and erlotinib) are chemotherapy (and radiation) sensitizers. They will cause unacceptable increase in morbidity/mortality when used with MTD (maximum tolerated dose of chemotherapy). We have recently publish a retrospective review on the three clinical trials of avastin in breast cancer that point to this activity. Note that in many of the recent clinical trials, the dose of chemotherapy is lowered in order to accommodate the synergistic action of these drugs.
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