How Genomics is transforming diagnosis and cancer treatment in modern era ?

 

Cancer is a disease caused by an abnormal proliferation of clonal cells caused by aberrations in the DNA. These can be seen in the form of mutations, deletions, substitutions, rearrangements, or amplifications which produces abnormal protein and function. These genetic alterations can be inherited or acquired due to environment factors like exposure to carcinogens, infections, life style etc.

The human genome project has estimated 80,000 to 1,00,000 genes in human, which are the functional unit of inheritance. Genomic information about cancer has revolutionized our understanding of cancer development and progression. The application of next generation sequencing has provided unprecedented opportunity to understand the biological basis of different cancer types.  This has led to better diagnosis and treatment strategies that are tailored to patient’s tumor, also known as precision medicine.

The main objective of genomics and precision medicine is to give the right diagnosis at the right time to choose the right treatment. Genomic sequencing solves the diagnostic dilemma in difficult cases on histopathology and helps to understand the genetic background of cancer patients. Patients with same type of cancer might respond differently to different drugs. Pharmacogenomics can also help to define the behavior of the tumor to a particular drug and helps to identify genomic biomarkers of drug response and resistance. By using genomic data and machine learning algorthims, one can accurately predict who will respond better and who will face the side effects of a particular treatment. Recently, robotics has been introduced which provides greater accuracy and expedites the process by automation of gene mapping and DNA sequencing.

Circulating tumor cells (CTCs) are molecular signatures of cancer cells that are shed from the primary tumor site, enter the circulatory system and are responsible for distant metastasis. This streamlines the monitoring of the patients to chemotherapy and radiotherapy. Cell free (cf) DNA helps in identification of the disease when the tissue biopsies are negative for tumor while PET CT shows hot spots of tumor nodules. Monitoring of minimal residual disease (MRD) by reverse transcriptase polymerase chain reaction (RT-PCR) in hematological malignancies helps to understand the response to targeted therapies. Some germline panels help to understand various syndromes like hereditary breast and ovarian cancers (HBOC) etc.  BRCA1 and 2 genes are involved in spectrum of diseases involving multiple organ system like female genital tract, breast, pancreas, prostate etc. FDA has approved Poly (ADP-ribose) Polymerase (PARP) inhibitors eg Olaparib has been proven to be of a great therapeutic value.  The targeted drugs act like small molecules, antibody based or direct inhibitors which block the gene expression, inhibit signaling pathway or aberrant protein expression.

Beyond the identification of targetable alterations, genomic methods can gauge tumor mutational burden (TMB), MSI and PDL-1 which might predict a therapeutic response to immune checkpoint inhibitors. Tumor agonistic or histology agonistic therapy for specific molecular fusions or alterations have revolutionized the therapeutic approach to tumors at different sites.

 “The Ultimate Validation of Genomics and Precision Oncology is when it gives a twinkle in patient’s eyes”

MY PET SNAIL ALBERT .

Today I am here to share a very unique experience about my pet snail...We brought him from a beautiful valley of Chikkamangaluru, Karnataka where we went for a holiday in 2018. One of the evening probably, we saw him crawling next to our door with a tiny head out of his tiny shell looking for a safe place to hide. We picked him and kept him in our room for two days and fell in love with this tiny creature of about one centimeter. So we brought him along with us to Bangalore in a small box within mud and few leaves to feed him on the way. We named him Albert because of our hypothetical guess of him being a male; only to learn later that snails are hermaphrodites ie they have both male and female parts and they can lay eggs on their own...!

As Albert grew, his shell became bigger, spiral and stripped; he actually grew into a handsome young man of around 12 centimeters long. He loved eating all types of vegetables, particularly the cabbage; slide into water bowl and would slug his slimy mascular body completely into the shell and slept for long hours. Albert would finish his tour sliding on the wooden cabinet and would show his beautiful double tentacles (we called them antennae...lol) which are known to be sensitive to smell. I would caress his shell every time I came back from work and he would brighten up and show his antennae, was among the most satisfying moment of my life...The thought that Albert recognizes me, he knows me filled me with joy and I accept that I loved him. 

It seems that snails body is attached to the shell and they cannot survive without their shells. Few small cracks can be plastered but loosing more than 60% of the shell is devastating. Just a week back, we found Albert on the floor with his shell broken and separated, probably from a fall during his little tour. He survived for four days, did eat and drink but his slimy body was getting dry and the shell couldn't be re-attached. We googled and found one rare unsuccessful surgery which happened in Israel. Albert died 3 days back, we gave him a proper burial in our garden and I kissed him Goodbye. 

I promise that even a smallest creature will find a way to communicate if we try to understand them. Albert did express his happiness and joy through his unique movement of antennae; and I found it very satisfying to understand him, feed him and clean him.  Its difficult to let go but sharing your emotions through writing definitely heals ! 

Thankyou for coming in our lives and giving us so much affection. Way to go Albert..!  

Amrit. 

Albert on his little tour !

Helping hearts !

I was blessed to be brought up in a convent school for almost a decade in a small town of Amritsar.  But I was very well aware of the inquisitive minds of less fortunate ones who couldn't attend school but had a deep yearning to learn more. My conscious mind realized the bitter truths and it changed me and I became more accommodative and proffered to the needs of others. And this reflected in my actions and teachings. It never occurred to me that I have to vanquish others to be a winner  !  

Well, I find quite surprising when I observe some senior professors embezzle the junior faculty for their narcissist egos. Few of my friends shared their stories that how their collaborative effort of writing books and papers was ripped apart after the work was completed. The post graduates made to do worthless jobs which gives them zero opportunity to grow. Another surprising fact I noticed seniors not sharing their knowledge because the brighter student threatens their position; which could be connected to a deep underlying sense of insecurity. 

Well everyone is different and are driven by different goals and motivations. But, everyone in the world needs help at some point and one must be lucky to get help at that time. But how many of us realize how magnificent it is to be able to provide help; give a helping hands to others who need it. 

I remember praying when I was small to help me understand better in school and I promised to help others in return. And this secret relationship between My GOD and me was the perfect world to live in as I always got rewarded. Probably, it was just a conscious or good will but it kept me going till today...

Love you all; the world is small and life is short; so lets make it a better place for everyone !