Targeted cancer therapy: An update

Antibody-drug conjugates: Potential game-changers

The science community often calls them ‘smart bombs’ or ‘biological missiles’. Antibody-drug conjugates (ADCs) may transform how we develop cancer drugs.

ADCs consist of three components: 

1. A monoclonal antibody (an immune system protein)
2. A tiny but potent cancer drug
3. A linker molecule

The antibody binds to antigens on cancer cells. Upon binding, the cancer drug destroys the cells, justifying the ‘missile’ label. This mechanism forms the basis of the ‘tumor-agnostic therapy’.

ADCs have shown promise for breast and ovarian cancer treatment. In the past six months, the Food and Drug Administration (FDA) has approved two ADC-based therapies: trastuzumab deruxtecan for HER-2-positive solid tumours, such as breast cancer, and enfortumab vedotin (Padcev, Astellas Pharma) plus pembrolizumab (Keytruda, Merck) for locally advanced or metastatic bladder cancer.

Combining ADCs with already-established treatments in oncology, such as chemotherapy, hormone therapy, radiotherapy, and immunotherapy, has the potential to improve patient outcomes. 

Immunotherapy: The future of precision treatment

Targeted immunotherapy has taken centre stage in cancer research and precision treatment. It works by activating the body’s own immune system against cancer. 

In the past decade, monoclonal or therapeutic antibodies have been a hot topic among cancer researchers. Other prospective targeted immunotherapies include checkpoint inhibitors, synthetic cytokines, cancer vaccines, and, more recently, chimeric antigen receptor (CAR) T-cell therapy. 

CAR T-cell therapy is known as a ‘living drug therapy’. It involves taking T-cells from a patient and engineering their structure. The modified T-cells are then reintroduced into the patient’s body, where they seek to attack the cancer cells.

Researchers have considered using CAR-T cell therapy as a one-time injection. This approach gives CAR T-cell therapy a huge advantage over conventional treatment. It prevents repeated therapy cycles and saves time and effort. 

That said, CAR-T cell therapy can also cause life-threatening side effects. A notable unwanted effect is cytokine release syndrome (CRS) in which cytokines flood the blood, causing high fever and severe hypotension. CAR-T cell therapy might also give rise to neurologic changes such as confusion, seizures and impaired speech.

The FDA has already approved CAR-T cell therapy for leukaemia, lymphoma, and multiple myeloma. Brain, pancreatic, and ovarian cancers are potential future candidates. 

Additional targeted drugs that have taken cancer research by storm include: 

• PARP (poly-ADN ribose polymerase) inhibitors for ovarian, fallopian tube, and peritoneal cancer
• Cancer growth blockers, such as EGFR and mTOR inhibitors

• Drugs that block new blood vessel formation (antiangiogenics), such as bevacizumab for metastatic colorectal cancer

The role of AI and next-generation sequencing

Artificial intelligence (AI) has put down roots everywhere. Oncology is no exception. Lately, AI has been used to improve next-generation sequencing (NGS). The automated AI algorithms are quick and effective at showcasing genetic variations. 

But what does this mean for targeted therapies? Well, by identifying genes responsible for cancer growth, AI helps scientists develop more precise drugs to target them. 

A recent study analysed the benefit of NGS in developing targeted therapies for lung adenocarcinoma. It highlighted this relationship as crucial for future discoveries.

Conclusion 

Targeted therapies and immunotherapies in oncology are developing at a fast pace. They give us hope that a cure for cancer is finally within reach.