**2. Challenges**

Though ACK1 is a therapeutic target for cancers, inflammation, immune and neurological diseases, very few inhibitors have entered the clinical trials. Hence there is urgent need to develop potential inhibitors. The *in vivo* pharmacokinetic properties of inhibitors also need to be improved. Some inhibitors have limited solubility in water which restricts the studies to be carried out on the animal models only. Due to the large distribution and participation of ACK1 in regulation of many signaling pathways, high specificity and precise positioning of inhibitors to diseased tissues are required, which increases the difficulty in drug designing. So, it is necessary to explore more biological functions of ACK1 and to verify the effectiveness of drugs *in vivo* and *in vitro*. As the inhibitors are developed by only limited methods (screening small molecules and fragment libraries), it have weak affinities which makes the selection of drug candidates difficult and time consuming. Further the development of allosteric inhibitors of ACK1 is also difficult as

#### *Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology DOI: http://dx.doi.org/10.5772/intechopen.102343*

it need full-length proteins in the biochemical analysis of ACK1, which is a great challenge as these proteins may exhibit aggregation, conformational changes and other phenomena, which are not possible for the *in vivo* and *in vitro* studies. In last 10 years, innovative immunochemotherapies have shown promising results in disease control rates but not survival. So, there is an acute need to develop novel drugs that can target dysregulated pathways in malignant tumors. Several functional challenges include the description of genetic abnormalities in the cancer kinomes and the recognition of accurate drivers which are accountable for tumor development. Only the precise analysis of the therapeutic involvement will indicate the clear role of kinases; as a tumor suppressor in non-cancer cells or a tumor mediator in cancer cells.
