Cancer drugs may not be working the way we think they work

Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered that many anti-cancer drugs do not work the way we think they work. The study, led by Jason M. Sheltzer, evaluated 10 anti-cancer drugs in the pre-clinical or clinical trials. Findings of this research may help in establishing more stringent tests for drugs before trying them on humans.

cancer colorful word in the wooden background

Sheltzer’s earlier investigations of a protein, MELK, paved way to this study. Several reports had suggested that MELK was essential for the survival of cancer cells. But Sheltzer found otherwise – cancer cells survived even in the absence of MELK. They also found that an anti-cancer drug (OTS167), which the clinicians claimed would target MELK, killed cancer cells that were depleted of MELK. Clearly, OTS167 did not target MELK to kill the cancer cells.

Sheltzer adopted this strategy to study more anti-cancer drugs. The team shortlisted 10 anti-cancer drugs that were in pre-clinical or clinical testing. They selected drugs that clinicians claimed would stop the proliferation of cancer cells by targeting a single protein. The researchers then deleted the gene that coded for the claimed target protein using the CRISPR-Cas9 technology and checked if the cancer cells survived. But cancer cells were killed. This suggested that the drugs were not targeting these proteins.

The researchers particularly studied a drug (OTS964) targeting the protein PBK in greater detail. They gave enough time for cancer cells to accumulate mutations and develop resistance to OTS964 to find what protein the drug targeted. Cancer cells are genetically unstable and accumulate mutations over time. These mutations, resulting in changes in the protein they code for, restrain the drug from binding to the target protein. Knowing the genes that are mutated help us understand the actual target proteins. On analysis, they found that the gene coding for CDK11 had several mutations in it. This indicated that CDK11 was the actual target of this drug.

This may be one reason why 97 per cent of cancer drugs tested in clinical trials do not go on to receive US FDA approval. Understanding the accurate ‘mode of action’ of a drug increases the chances of its success. It is possible that the earlier experimental methods of inhibiting a gene or protein – RNAi and small molecule inhibitors – could be blocking some other protein in the cell. This may well the reason why drugs work differently than how we thought they would.

With advanced technologies like CRISPR-Cas9 technology, we can be more accurate. As the current study showed, this can be used as a method to test the claimed “mode of action” of the drug before they are tested on humans. This study also gives us a method to understand what proteins or genes are essential for the survival of cancer cells.

Pic Courtesy: China Daily

Book Review: Gene Machine by Venki Ramakrishnan

There are great scientists; there are prolific writers. But a combination of these traits is rare to find. Venki Ramakrishnan emerges as one of this rare kind in his first book “Gene Machine”.

In his book, Venki walks us through a gripping account of his illustrious academic career. He opens by recounting his indistinct graduate life and describes how things turn around on meeting his life partner, Vera Rosenberry. He then narrates how he stumbles upon the Ribosome and sticks to it even when it goes out of fashion.

In the chapters that follow, Venki describes how he takes small steps toward the big problem and jumps right in at the right time. He is honest about the general factors that helped him in his academic journey – being in the right place at the right time, having a great scientific network, and luck.

Venki presents complex biological concepts, devoid of jargons, in a way that is both relatable and understandable. He explains the deciphering of ribosomal structure with an overarching illustration of an alien trying to understand how a car works.

What is exemplary about Venki, as he comes across in this book, is his objective descriptions of his students, fellow scientists, and competitors. He never discredits his competitors, but plainly describes their contributions. In one of the chapters, he explains the contributions of leading scientists in the field to an award committee member.

The book is divided into twenty chapters, my personal favourite being “Coming out of the Closet”. Overall, Venki engages his readers in a special way with his elegant writing and intact element of suspense. His writing reflects his true self – emotions of excitement, anxiety, irritation, ego, and frustration. In the end, he is also quite frank about the politics of recognition and how big prizes corrupt scientists.

Overall, the book is totally worth the read – engaging, enjoyable and inspiring.

The little joys of life

Escalator   kids wonder

One city that will stay close to my heart for a lifetime is the city of Chennai. It has given me memories and experiences some of which I will cherish for a very long time. Although I went to Chennai with the intent of being trained to be researcher, the city taught me many more things. From financial management to disaster management, Chennai gave me some extra coaching.

What I am about to tell you is a small incident that I witnessed in Chennai. It is something that we might just shrug off, but somehow it stayed in my heart.

On one of the extended weekends, I was heading home from Chennai. As I got off the suburban train and made my way to the central railway station, I saw a little boy and his excitement about life. As I followed the crowd that waited to get on the escalator, I heard him shout in excitement “Look Dad, the stairs are moving! We don’t have to climb them, they’ll do it for us!” He kept repeating it as he stood on the escalator, amazed at the way it worked.

I stood behind the kid and wondered about the little joys that we have in life. Remember the day you stepped in an elevator for the first time? Or used a smartphone or a social network? Didn’t we all have that excitement in us? Over time, with progressive acquaintance, we tend to lose that sense of wonder. We get bored of it. The same things that once filled us with excitement turns out to be regular and unexciting. That is why it is important that we absorb things slowly in life. That will help us sustain the sense of wonder. When such exciting things come our way, let us relish it, for these are the little joys of life – the spice in our savory!

Life as a student teacher

      

Student-teacher! An oxymoron, right? Well, my life has been it for over a year now. I’ve been helping teachers conduct some laboratory courses for the third and fourth year B. Tech students. Although at times it feels terrible to slog for more than what you get, it has been rewarding in many ways. Of the few good memories of this place that I would cherish, my life as a student-teacher undoubtedly forms a big part! Of course, I don’t have to explain it when I am actually writing this article at the time that I’m supposed to be writing the thesis.

Although I have been passionate about teaching since my undergraduate days, I had never thought that teaching could be so rewarding. Being a student-teacher was all the more exciting! It was amazing to interact with the juniors whom I taught. Perhaps the rapport between us was strong because they considered me a senior student rather than a conventional teacher. Of course, I felt the same about them. They were my juniors and friends, and then my students.

While I believe that classroom learning in this setting was fun, I think I was also able to extend the friendship beyond the boundaries of the class. Despite having an unbiased perception of each student on academic grounds, I felt a greater connect with some beyond the classroom. I had the opportunity to interact with different people at different levels and these are memories that I will treasure for a very long time! Outside the lab, I had been (and still am) a friend (I suppose) to many of them talking about random stuff, taking part in co-curricular activities, or playing sports with some of them. These were people who were like an oasis in a desert, a source of comfort and an indication that sometimes the best things could happen to you even at the worst times or places!

To put it plainly, I’m going to miss you guys as I graduate from here. I’m going to miss those teaching-learning-cribbing-talking-laughing moments! The drama queens, and my badminton buddies (you know who you all are) – I must say that you are the ones that I will miss the most! Ankit, Ankita, Sakkeeshya, Jeson, Manjusha, Femina, Jismi, Akshay, Kishore, Mithil, Anusha, Manish, Vivek, Sreeja, Upasana, Aishwarya – this goes to you all as well, for you all put a smile on my face knowingly or unknowingly! You all mean much more than just random juniors to me.