Current Trends and Our Own Efforts in Cancer Therapy

The addiction of many tumors to their driver mutations (i.e., oncogenes) exposes critical vulnerabilities, which might be exploited by pharmacological strategies. In addition to ‘oncogene addiction’, cancer drugs may target non-oncogene addictions, primarily survival pathways characteristics to low-grade, hormone-, or growth factor-dependent tumors. Examples include the estrogen receptor in breast cancer and EGFR in colorectal cancer.

The tumor microenvironment (TME), a collection of non-tumor cells embedded in the vicinity extracellular matrix and blood vessels, has provided additional opportunities. Unlike tumor cells, which constantly acquire new mutations and they display clonal heterogeneity, the TME is genetically stable and its clonal structure might be simpler. Agents targeting the endothelium and suppressing angiogenesis, as well as antibodies targeting immune checkpoints exemplify the potential of TME-directed drugs.

The currently available armamentarium of medical oncologists includes >100 clinically approved drugs (excluding . Because more than one third comprises kinase inhibitors and the other third contains monoclonal antibodies, it is logical assuming that combinations of antibodies and kinase inhibitors will become a mainstay in oncology. Our own studies focus on EGFR-specific kinase inhibitors: three generations of quite effective inhibitors have been approved for the treatment of non-small lung cancer, but emergence of resistance preempts further treatment with third generation drugs. I will describe an alternative approach that combines antibodies and kinase inhibitors, and effectively inhibits all mutant forms of EGFR.