<h3>Title</h3>
<h3>Addressing resistance and selectivity issues of metal-based chemotherapeutics through drug design</h3>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p>Cancer is the second leading cause of death in the world. It originates from uncontrolled cell growth in abnormal tissues either as a result of DNA mutations or because of inherited faulty genes. Current major clinical treatments for cancer include surgery, chemotherapy, radiation therapy, and in special cases endocrine therapy and immunotherapy. Among these, chemotherapy remains the most widely used treatment modality and particularly, platinum-based drugs remain the most successful clinically used therapeutic drugs<a href="#_ftn1" name="_ftnref1">[1]</a>. Three platinum-containing drugs are approved worldwide for treating cancer in humans, i.e. cisplatin, carboplatin, and oxaliplatin. Though platinum compounds  are very successful in the clinic<a href="#_ftn2" name="_ftnref2">[2]</a> and widely used against various cancers, they suffer from two major drawbacks: 1) severe side effects and 2) emergence of resistance by the cancer cells.<a href="#_ftn3" name="_ftnref3">[3]</a> Since their discovery, tremendous efforts towards optimization of the drug response have gone into making these platinum drugs safer for patients, in particular, reducing the unpredictable side effects like severe neuro- and nephron-toxicity.<a href="#_ftn4" name="_ftnref4">[4]</a> A second major, ongoing, initiative is to overcome tumor resistance to antiproliferative activity of platinum. These two issues are a major hurdle in the discovery of new and improved chemotherapeutics. In the last 10-15 years, the scientific community has been looking at alternate pharmacophores - ruthenium, iridium, and bimetallic compounds including platinum that can address these issues. They exert different modes of action and result in improved selectivity towards cancer cells as well as overcome the platinum resistance. Nevertheless, the improved results are primarily restricted to <em>in vitro</em> assays and further evidence for their activity (<em>in vivo</em>) is still missing. During the last one year, we have worked on the synthesis of a wide range of organometallic compounds belonging to broadly 4 categories based on structural features of the compounds (Figure 1). We have showed through elaborate <em>in vitro</em> experiments that they exert either better or extremely high anticancer efficacy when compared with clinical platinum drugs and use a different mechanism of action for the same. Simultaneously, they are able to address issues of selectivity and resistance. Finally, we have proved their ability to suppress tumor growth <em>in vivo</em> xenograft model experiments with mice, showcasing their high potential to be developed as next generation anticancer drugs.</p>
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