I embarked on my oncology career in 1974, a time when medical oncology was only just finding its footing in India. In fact, the country's first dedicated Medical Oncology unit had only been established a few years prior, in 1971, at the Cancer Institute in Chennai. Back then, our treatment arsenal was limited to nitrogen mustard, 6-MP, prednisolone, 5-FU, endoxan, methotrexate, and vincristine. Cancer treatment at that time was primarily surgery and radiotherapy. Subsequently, the introduction of combination chemotherapy and adjuvant chemotherapy played a major role in improving outcomes in many cancers.

In those years, drug discovery methods were largely serendipitous, with landmark discoveries like cisplatin, anthracyclines, taxanes, gemcitabine, ifosfamide, and etoposide. Another pivotal breakthrough of this era was the concept of combination chemotherapy, which resulted in cures for many lethal diseases, including acute lymphoblastic leukaemia, Hodgkin’s lymphoma, Wilms’ tumour, germ cell tumour, Ewing’s sarcoma, and osteogenic sarcoma. The concept of adjuvant chemotherapy further improved outcomes in breast cancer, ovarian cancer, and colorectal cancer. Several cancer types benefited significantly during this era from these chemotherapy combinations. Hodgkin’s lymphoma became routinely curable with regimens like MOPP and, soon after, ABVD. Paediatric leukaemias saw remission and cure rates climb sharply with multi-agent protocols. Testicular germ cell tumours transformed from a near-certain death sentence to a highly curable disease with cisplatin therapy.

Alongside chemotherapeutic advancements, improvements in supportive care contributed to better outcomes. The Cancer Institute in Chennai established the country's first Blood Component Unit in 1971. The availability of blood components, haematopoietic growth factors, antibiotics, antifungal and antiviral medications, and modern, effective antiemetic therapies paved the way for high-dose chemotherapy and autologous/allogeneic stem cell transplantation.

A monumental development in India during this era was the advent of bone marrow transplantation. I had the opportunity to train in bone marrow transplantation at Fred Hutchinson Cancer Center under Dr E. Donnall Thomas, a Nobel Laureate who performed the world's first bone marrow transplant. At Tata Memorial Hospital, we performed India's first bone marrow transplant in 1983 for a young girl with acute myeloid leukaemia, which was successful. This paved the way for bone marrow transplantation in the treatment of many haematolymphoid disorders.

During the late 1980s and early 1990s, we witnessed the early signs of a shift toward rational, biology-based drug development with agents like tamoxifen and ATRA, which changed the therapeutic landscape in HR-positive breast cancer and APML, respectively. I remember being amazed by this concept - it was a glimpse into the future, showing that understanding cancer biology could directly lead to cures. However, for most cancers in the 1980s, our therapies were still largely cytotoxic drugs discovered through traditional means, and the real wave of targeted therapies was yet to come.

The discovery of rituximab in 1997, trastuzumab in 1998, and imatinib in 2001 revolutionised cancer treatment, dramatically transforming outcomes in non-Hodgkin lymphoma, HER2-positive breast cancer, and CML, respectively. As an oncologist witnessing these breakthroughs, it felt almost miraculous: after decades of relying on nonspecific cytotoxic drugs, we finally had agents that targeted cancer-specific pathways. The old paradigm of “one size fits all” was being replaced by “the right drug for the right target.”

As a result of these advances, the drug discovery paradigm began to shift. Pharmaceutical research in the 1990s increasingly focused on identifying molecular drivers of cancer (receptors, oncogenes, angiogenic factors) and designing drugs to block them. In lung cancer, outcomes were transformed by the development of tyrosine kinase inhibitors targeting EGFR, ALK, ROS1, BRAF, MET, and RET. This rational approach was enabled by advances in cancer biology – the discovery of tumour suppressor genes, improved understanding of cell signalling pathways, and tools like PCR and DNA sequencing to detect genetic mutations.

During this decade, the concept of precision medicine became ingrained in everyday practice. We began routinely testing tumours for molecular markers to guide therapy: HER2 in breast cancer (to decide on trastuzumab), KRAS mutations in colon cancer (to determine the efficacy of EGFR antibodies), KIT mutations in gastrointestinal stromal tumours (to predict sensitivity to imatinib), and later EGFR mutations in lung cancer (to select patients for EGFR inhibitors). The mapping of the human genome in 2003 ushered in an era of genomic tools that gradually became integral to oncology; by the late 2000s, multi-gene panel assays were in development, foreshadowing the next wave of personalized therapy. I recall my first lung cancer patient (around 2006) who tested positive for an EGFR mutation – we treated her with gefitinib, and she experienced a dramatic remission of her lung metastases. Such experiences reinforced the power of matching treatment to tumour biology.

Cancers benefiting most from targeted approaches between 2000–2010 included CML, which became the poster child for targeted therapy. Long-term results from the IRIS trial showed that over 80% of CML patients on imatinib achieved durable remissions, turning a once-fatal disease into one that many could live with for decades. Gastrointestinal stromal tumours, previously resistant to chemotherapy, were transformed by imatinib into a largely curable disease. HER2-positive breast cancer outcomes improved substantially with trastuzumab; even patients with metastatic disease were living significantly longer, and cure rates in early-stage disease improved with combined chemotherapy and trastuzumab. In lung cancer, patients with EGFR mutations or ALK rearrangements exhibited extraordinary responses to targeted TKIs, improving overall survival. In colorectal cancer, median survival in metastatic disease extended beyond two years (compared to roughly one year in the 1990s) with the addition of targeted drugs like bevacizumab and cetuximab. Multiple myeloma underwent a paradigm shift with the introduction of the proteasome inhibitor bortezomib (2003) and the immunomodulator lenalidomide (2006), producing deep responses and prolonged survival, especially when combined with autologous transplantation.

If the 2000s were the era of targeted therapies, the 2010s will be remembered as the era of immunotherapy. Having lived through the chemotherapy and targeted therapy revolutions, seeing immunotherapy take centre stage was nothing short of astonishing. In 2011, the first immune checkpoint inhibitor (ipilimumab, an anti-CTLA-4 antibody) was approved, improving survival in metastatic melanoma – a cancer that previously had a median survival of only months. This was followed rapidly by PD-1 inhibitors (pembrolizumab and nivolumab) around 2014–2015, which produced durable tumour responses in melanoma, lung cancer, kidney cancer, and other malignancies. I clearly remember a patient I treated in 2015 for epithelial ovarian carcinoma. The idea that we could unleash a patient’s own T-cells to control advanced cancer – sometimes leading to complete, lasting remissions – felt like science fiction turned into reality. I treated a metastatic melanoma patient in 2015 with nivolumab; two years later, he had no visible tumour on his scans. Such cases were rare but proved that even stage IV cancer could sometimes enter long-term remission with immunotherapy.

Equally transformative during this decade was CAR T-cell therapy, which emerged as a revolutionary treatment. By 2017, CAR T-cell therapies (engineered T-cells targeting CD19 on leukaemia/lymphoma cells) were approved in the US and Europe, curing some patients with otherwise incurable leukaemias and lymphomas. In India, we followed these developments keenly and aspired to bring them to our patients. By 2021, India conducted its first CAR T-cell therapy trial (at Tata Memorial Hospital in Mumbai) using an indigenously developed product. By late 2023, this homegrown CAR-T (NexCAR19) became the first approved CAR-T therapy in India - achieved at a fraction of the cost of imported products and a proud example of local innovation making advanced therapy more accessible.

The approach to drug discovery in the 2010s was heavily driven by biology and genetics. Comprehensive genomic profiling of tumours became feasible and increasingly routine for certain cancers. We could send a patient’s tumour sample for next-generation sequencing and identify specific mutations or gene fusions to target. The FDA began approving treatments based on molecular profiles rather than tumour origin - for example, pembrolizumab was approved in 2017 for any MSI-high cancer, regardless of tissue type, and drugs like larotrectinib were approved for any tumour with an NTRK gene fusion. This “tumour-agnostic” therapy concept underscored the shift to treating the cancer’s biology first and location second. We also witnessed the rise of AI and big data approaches, with researchers using machine learning to analyse genomics and clinical data to identify new drug targets or predict responses – early steps that may shape the next decade of discovery.

Current Reflections & Future Directions

Standing now in the mid-2020s, reflecting on this 51-year journey, I am filled with both pride and humility. Medical oncology in India has evolved from a nascent discipline in the 1970s to a sophisticated, cutting-edge field today, closely integrated with global research and innovation. We have gone from an era when only a few cancers were treatable to an era when many cancers are chronically manageable or even curable. Treatments that were once science fiction - sequencing a tumour’s DNA to select therapy or genetically re-engineering immune cells to attack cancer - are now part of routine practice in leading centres. The result is that patients who once had no chance are now living for years or decades with cancer, often with a good quality of life. Another major innovation has been the reduced toxicity of modern targeted and immunotherapy approaches. As genomic sequencing becomes more affordable, we will likely see even more personalized therapy - perhaps one day every patient’s tumour will be molecularly profiled to create an individualized treatment plan.

Importantly, I believe the human touch in oncology will remain paramount. Our patients have taught us that compassion and hope must accompany science. No matter how advanced our treatments become, taking the time to counsel patients and address their emotional needs will always be a cornerstone of good practice.

My five-decade journey in oncology has shown me that progress is a marathon, not a sprint - it requires sustained effort, adaptability, and the collective efforts of doctors, researchers, policymakers, and the public. I am confident that with continued innovation and a focus on equity, the future of oncology in India will be bright, bringing hope to every patient who walks through our clinic doors.