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 produce abnormal protein and function. These genetic alterations can be inherited or acquired due to environmental factors like exposure to carcinogens, infections, lifestyle etc.

The human genome project has estimated 80,000 to 1,00,000 genes in humans, which are the functional unit of inheritance. Genomic information about cancer has revolutionised our understanding of cancer development and progression. 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.

DNA sequencing of the tumour is increasingly used, most often in patients with advanced metastatic disease. Next generation sequencing has provided an unprecedented opportunity to understand the biological basis of different cancer types by enabling us to determine mutations, copy number variations (CNV) and translocations at the same time generating data in terabytes of millions of reads of genomic DNA. By using genomic data and machine-learning algorithms, one can accurately predict who will respond better and who will face the side effects of a particular treatment.

Recently, bioinformatics and robotic technology has been introduced which provides greater accuracy and expedites the process by automation of gene mapping and DNA sequencing. Pharmacogenomics can also help to define the behaviour of the tumour to a particular drug, and helps to identify genomic biomarkers of drug response and resistance, as the same type of cancer might respond differently to different drugs. This has led to better diagnosis and treatment strategies that are tailored to the patient's tumour, also known as “Precision medicine”.

Germline testing (done on cells that do not have cancer, to see if a person has a gene mutation that is known to increase the risk of developing cancer) and genetic counselling are recommended for patients with cancer who have the disease at an early age and with multiple family members affected by same or related cancers.

Many germline cancers including hereditary breast and ovarian cancers (HBOC), hereditary non polyposis colorectal cancers (HPNCC), BRCA 1 & 2 etc. have been reported to be quite common in India. People who show positivity for the inherited mutations in the BRCA1 or BRCA2 genes are at 45% to 65% risk of developing breast cancer and 10% to 20% risk of developing ovarian cancer by age 70. BRCA1 and 2 genes are involved in a spectrum of diseases involving multiple organ systems like the female genital tract, breast, pancreas, prostate etc.

The detection of either inherited germline variants or acquired somatic variants in the patient can help in selecting systemic therapy and as a screening tool in patient relatives might help in preventive surveillance, adopt a healthy lifestyle by avoiding the risk factors.

However, both germline and somatic biomarker testing (testing done on cancer cells, to learn more about the cancer) are complementary, and different recommendations can follow from each. FDA has approved Poly (ADP-ribose) Polymerase (PARP) inhibitors e.g. Olaparib for HBOC has been proven to be of 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.

Liquid biopsy (cell free (cf) DNA) is a non-invasive method of sampling to analyse circulating tumour cells (CTCs), which are shed from the primary tumour site into the circulation and can be used where tissue biopsy is not available. These molecular signatures of cancer cells are routinely being used for diagnosis of cancer, long-term monitoring of tumors with resistance mutations.

This streamlines the monitoring of the patients to chemotherapy and radiotherapy. Monitoring of minimal residual disease (MRD) by RT-PCR in hematological malignancies (cancer in blood-forming tissues) helps to understand the response to targeted therapies.

Beyond the identification of targetable alterations, genomic methods can gauge tumour mutational burden (TMB), microsatellite instability (MSI) and programmed cell death (PDL- 1) which might predict a therapeutic response to immune checkpoint inhibitors. Tumour agonistic or histology agonistic therapy for specific molecular fusions or alterations have revolutionised the therapeutic approach to tumours at different sites.

As responsible citizens, we must take a leap towards cancer care by listening to our body and look for irregularities by getting tested. Health care will keep innovating and will beat the disease in solidarity for the healthier world.

(The author is a doctor at Kokilaben Dhirubhai Ambani Hospital, Mumbai)