When people think of the deadliest diseases, their mind jumps to the most commonly heard incurable illness (if not treated on time) called CANCER. The side effects occurring due to the cancer treatment also make it quite painful for the patients. But researches are going on in several parts of the world. We bring you a research work done by Dr. Kausar Raza, working at the California Institute of Technology (Caltech) in the United States as a postdoctoral research fellow. Here are the excerpts of the interview.
Q. Please give a brief explanation of your research.
Ans. My research interest mainly focuses on locating the lesions with the help of [4Fe4S] cluster and their treatment using Pt-based anti cancer agents. The research area is divided into two parts: (i) Investigating the chemical role of [4fe4S] cluster in eukaryotic proteins through electrochemical and biochemical studies. (ii) Use of Pt-based complexes for chemo phototherapeutic treatment of cancer.
Cancer is considered one of the deadliest diseases outspread in various parts of the human body. Different methodologies have been implemented to date to fight against the proliferation of cancerous cells, namely, Chemotherapy (mainly Pt-based anticancer drugs), Photodynamic Therapy (which involves photosensitizer, light, molecular oxygen), etc. To fill the pitfalls of conventional chemotherapeutic and photodynamic therapeutic drugs, including the NER machinery and less tissue penetration, respectively, during my Ph.D. research at the Indian Institute of Science, Bangalore, I combined these two well-known methods modalities. Chemotherapy and photodynamic therapy (PDT) by tuning the structural properties of Pt-based complexes to kill the cancer cells selectively. The idea was to develop the series of conjugates bearing the structural framework of the conventional chemotherapeutic anticancer drug, cisplatin, and BODIPY dyes for PDT activity.In photodynamic therapy, the growth of cancer cells can be terminated in the presence of light which generates ROS (reactive oxygen species) capable of cleaving the DNA of the tumor cells and causing cell death. Cell imaging is beneficial to track cancer/lesion sites inside the human body. The combination of the Pt metal encrusted the path for DNA cross-linking and the BODIPY motif attached which aided in cell imaging and killing of cancer cells in the presence of light, comes out as a new scope to design the more efficient photodynamic chemotherapeutic anti cancer agents.
Earlier in my Ph.D., I have tried to treat cancer; now, I am exploring my research to detect lesions through DNA mediated charge transport chemistry. It focuses on assessing the functional role of iron-sulfur [4Fe-4S] in eukaryotic DNA replicative and repair proteins. We perform the electrochemical investigation to detect the tumor/disordered sites using DNA-mediated electron transfer.
Q. What was the objective of your research?
Ans. Since various anticancer drugs are known to treat numerous kinds of cancers, namely colorectal cancer, breast cancer, oral cancer, lung cancer, etc. I aimed to design and synthesize a highly selective drug towards killing the cancer cells without harming the normal living cells. We intended to approach a dual-action mechanism of platinum-based anti cancer drugs for accurate time tracking and selective cancer cell death.
Q. What were the findings of your research?
Ans. We prepared a series of monofunctional Pt-based complexes capable of binding with DNA for the treatment against cancer. We have mainly designed the mitochondrial targeting anti cancer drugs, as mitochondria are the cell’s powerhouse and lack NER machinery. The significant outcome of our studies is in the form of an indigenously synthesized prodrug with 100-fold better anti cancer activity than the FDA-approved Photofrin drug. Moreover, this drug can be tracked inside the cell, which is not the case with any FDA-approved platinum-based anti cancer drugs. We have conducted the in-vivo anti cancer studies of these drugs in the living mice models using photodynamic chemotherapeutic dual action mechanism and obtained promising results that are a patent in this emerging field. This work was done with collaboration in the department of biological sciences at IISc.
This study provides further scope for combinatorial research that includes photodynamic therapy and DNA cross-linking ability of the monofunctional Pt(II) drugs (Chemotherapy) against cancer. Finally, the in vivo assay results on mice showed the significant arrest of tumor growth and its shrinkage in size, thus giving new insights into the chemistry of platinum-based PDT agents.
Q. Any scholarships or awards for research?
Ans. I have received the prestigiousCarl Storm International Diversity (CSID) fellowship for Gordon Research Conference (GRC), Metal in Medicine, USA. I am also a recipient of “Government of India International Travel Research Award (DST), CSIR Travel Research Award, ICMR Travel Research Award, SBIC Student Travel Grants for ICBIC-19 in Interlaken, Switzerland. I received a fellowship from MHRD and CSIR for five years during my Ph.D.
Q. How do you think your research would be beneficial to Society?
Ans. Cancer counts among the second deadliest diseases in the world. About 30% of India’s affected population accounts for oral cancer only among all types of cancer. Among the various therapies established for cancer treatment, photodynamic therapy is well known for treating oral cancer. My research on Pt-based drugs will provide new insight and scope to combine the two therapies and kill the tumor with notable potency.
Our mice model demonstrated an excellent efficacy of our drug inside the living being. These new findings can lead to investigating the drug-tumor interaction inside the human body. Implementation of our Pt-based prodrugs will provide a new way to treat cancer. Moreover, commercializing these drugs may reduce the cost of treatment. In addition, it’s manufacturing at the industrial level will increase the employment for several educated and skilled people in our country.
Q. Give some suggestions to the budding scientists.
Ans. Do not hesitate while expressing and talking about yourself, be it stress or mental health imbalance. Also, create another world outside the lab and explore it. Establish a name for yourself. Above all, perhaps, to be successful in academia, you need to develop your persistence and preserve your creativity no matter what. The key to unlocking the untapped potential is to create and build a path conducive to novelty in science. Make your research plans wisely and execute them in a disciplined way. Always remember, slow and steady wins the race.