The Science Behind Cancer Therapies

Cancer, a complex group of diseases, is caused by uncontrolled cell division. It is often characterized by the potential to invade or metastasize to other tissues, and remains one of the leading causes of death worldwide. The heterogeneity of cancer, encompassing hundreds of distinct subtypes with varied molecular profiles, presents immense challenges for effective treatment. However, over the past century, we have witnessed an evolution of cancer therapy, from crude cytotoxins to precision-guided biological interventions, this has transformed patient outcomes in many contexts. In this article, I’ll delve into the science of major current cancer treatments, including chemotherapy, radiation, immunotherapy, and CAR-T cell therapy. I’ll also examine how genetic and lifestyle factors contribute to cancer risk, and highlight promising avenues in ongoing research.

Chemotherapy refers to the systemic administration of cytotoxic agents that target rapidly dividing cells. Most chemotherapeutic drugs, such as alkylating agents (e.g., cyclophosphamide), antimetabolites (e.g., 5-fluorouracil), and anthracyclines (e.g., doxorubicin), act by interfering with DNA replication or mitotic processes, where the uncontrolled division stems from. These agents are non-specific, affecting both cancerous and normal proliferative cells, notably those in the gastrointestinal tract, bone marrow, and hair follicles. This lack of selectivity accounts for common side effects such as immunosuppression, mucositis, alopecia, and nausea. Resistance to chemotherapy, through mechanisms such as increased drug efflux (e.g., P-glycoprotein expression) or DNA repair upregulation, remains a central barrier to efficacy and often drives treatment failure in relapsed cancers.

Radiation therapy (RT) uses ionizing radiation, X-rays or gamma rays, to induce double-stranded DNA to break within tumour cells, leading to apoptosis or mitotic catastrophe, two forms of cell death. There are two primary delivery methods: external beam radiation therapy (EBRT) and brachytherapy, where radioactive sources are placed close to or within the tumour. RT is especially effective for localized tumours and is often employed in adjuvant or palliative settings, where RT is employed after a primary treatment to avoid reoccurrence of cancer or when the treatment is used in terminal patients to avoid spread and improve the quality of life left. The biological effectiveness of RT is modulated by fractionation, oxygenation status (hypoxic tumours are more resistant), and the DNA repair capacity of the targeted cells. Advances such as intensity-modulated radiation therapy (IMRT) and proton therapy have improved the spatial precision of dose delivery, minimizing collateral damage to surrounding healthy tissue.

Immunotherapy represents a paradigm shift in cancer treatment by using the patient’s immune system to detect and destroy malignant cancerous cells. One of the foundational strategies involves immune checkpoint inhibitors (ICIs), which target negative regulators of T-cell activation, such as PD-1, PD-L1, and CTLA-4. These molecules are often exploited by tumour cells to evade immune detection. Blocking them can unleash a potent antitumour immune response, particularly in immunogenic cancers like melanoma and non-small cell lung cancer. However, only a subset of patients exhibit durable responses, and immune-related adverse events (irAEs) ranging from dermatitis to autoimmune colitis reflect the fine balance between tumour suppression and immune tolerance.

Chimeric Antigen Receptor T-cell (CAR-T) therapy is one of the most promising forms of adoptive cell transfer in oncology. In this technique, T-cells are extracted from a patient and genetically modified ex vivo, meaning outside of the patient, to express synthetic receptors that recognize specific tumour-associated antigens, such as CD19 in B-cell cancer growths. Upon injection, these engineered T-cells find and destroy cancer cells using the target antigen. Clinical trials and approved therapies, such as tisagenlecleucel and axicabtagene ciloleucel, have demonstrated profound responses in refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. However, challenges such as cytokine release syndrome (CRS), neurotoxicity, and limited efficacy in solid tumours persist. Ongoing research in this field, focuses on improving CAR constructs, optimizing antigen selection, and modulating the tumour microenvironment to enhance T-cell infiltration and persistence.

The science behind cancer treatments: from chemotherapy to CAR-T and more

Chemotherapy

Radiation Therapy

Immunotherapy

CAR-T Cell Therapy

Genetic Influence on Cancer Risk

Lifestyle and Environmental Factors

Personalized Medicine

Cancer vaccines

Nanomedicine

Artificial Intelligence and clinical data

Cancer arises from accumulated genetic alterations that disrupt normal cell cycle regulation, apoptosis, and genomic stability. Inherited mutations in tumour suppressor genes, such as BRCA1/2 (breast and ovarian cancer) and TP53 (Li-Fraumeni syndrome), significantly elevate lifetime cancer risk. These germline mutations, mutations in reproductive cells, are complemented by somatic mutations, mutations in non-reproductive cells, acquired over time due to environmental insults or replication errors. Advances in next-generation sequencing have uncovered common cancer-causing mutations, like those in the KRAS, EGFR, and BRAF genes, as well as major DNA rearrangements, such as the BCR-ABL fusion. These genetic changes not only fuel tumour growth but also offer specific targets for treatment. In addition, changes in gene regulation, like DNA methylation or modifications to histone proteins, proteins that provide structural support to chromosomes by packaging and organizing DNA, can disrupt normal cell function and lead to cancer, even without altering the DNA code itself.

While genetics plays a critical role, lifestyle and environmental exposures substantially influence cancer risk. Tobacco use remains the most preventable cause of cancer worldwide, strongly associated with lung, head and neck, and bladder cancers. Diets high in red and processed meats, alcohol consumption, physical inactivity, and obesity have all been linked to increased risk through mechanisms involving chronic inflammation, hormonal imbalances, and oxidative stress. Infectious agents such as human papillomavirus (HPV), hepatitis B and C viruses, and Helicobacter pylori are connected to cervical, liver, and gastric cancers, respectively. Public health interventions, like vaccination programs (e.g., HPV vaccine), smoking reduction campaigns, and cancer screening, have significantly reduced the burden of preventable cancers. Smoking rates in the UK have significantly declined since the link between smoking and lung cancer was established in the 1950s. In the early 1950s, approximately 80% of men and 40% of women in the UK were smokers. By 1998, these figures had dropped to 26% for men and 23% for women. This decline is attributed to increased awareness of the health risks associated with smoking, public health campaigns, and tobacco control policies. Although even today these figures aren’t at 0, as a society we’ve made huge progress. Due to the addictive nature of nicotine, we cannot expect these statistics to drop any lower soon.

Personalized or precision oncology aims to tailor therapy based on the molecular characteristics of an individual’s tumour. Gene profiling can identify mutations (e.g., EGFR mutations in lung adenocarcinoma or HER2 amplification in breast cancer) that guide the use of targeted therapies such as tyrosine kinase inhibitors and monoclonal antibodies. Liquid biopsies, which detect circulating tumour DNA (ctDNA) in the blood, are emerging tools for real-time monitoring of treatment response and minimal residual disease. Personalized approaches enhance efficacy and reduce unnecessary toxicity, although challenges remain in addressing tumour heterogeneity and resistance mechanisms. Dr. James P. Allison, Nobel Laureate in Physiology and Medicine 2018, discussed the future of combining immunotherapy with precision cancer therapeutics to design individualized therapies in an interview with the American Association for Cancer Research (AACR). He emphasizes the importance of combining different therapeutic approaches to tailor treatment to individual patients.

Brief cancer treatment timeline:

• 1890s: Surgical excision of tumors
• 1940s: Introduction of nitrogen mustards (early chemotherapy)
• 1950s: Development of radiation therapy machines
• 1970s: Discovery of oncogenes
• 2000s: Approval of monoclonal antibodies (e.g., trastuzumab)
• 2017: First FDA approval of CAR-T therapy
• 2020s: Rise of AI, liquid biopsies, and personalized oncology

Cancer vaccines can be categorized as prophylactic (e.g., HPV and HBV vaccines) or therapeutic. Therapeutic vaccines aim to stimulate an immune response against established tumours by introducing tumour-associated antigens or neoantigens. Experimental vaccines, such as dendritic cell vaccines like the Sipuleucel-T for prostate cancer, are being tested on various cancer growths. Success is contingent on how well the vaccine targets a specific cancer antigen, how strongly it activates the immune system, and whether it can overcome the strategies tumours use to hide from our immune system, as to not trigger a response.

Nanotechnology in oncology uses nanoparticles to deliver chemotherapeutic drugs directly to tumour cells, improving drug solubility, stability, and bioavailability. These carriers, such as liposomes, dendrimers, and polymeric nanoparticles, can be modified to carry specific binding molecules that target cancer-specific receptors, enhancing selectivity. Approved examples include liposomal doxorubicin (Doxil) and albumin-bound paclitaxel (Abraxane). Ongoing research aims to refine nanocarriers that respond to tumour microenvironmental cues, like pH and enzymes, for controlled drug release.

AI is revolutionizing cancer diagnostics and treatment planning. Machine learning algorithms can detect subtle patterns in radiologic images and histopathology slides, improving early detection and subtype classification. Integrating multi-omics data, where different types of data, like genomics, transcriptomics, proteomics, is combined during analysis, through AI, enables the identification of biomarkers and therapy targets. Predictive modelling assists oncologists in estimating treatment responses and prognoses. Ethical considerations, such as data privacy and algorithm transparency, remain critical as AI becomes more embedded in clinical oncology.

The science of cancer treatment has progressed from nonspecific cytotoxic strategies to highly personalized interventions rooted in molecular and immunologic research. Chemotherapy and radiation remain widely used, yet are now often supplemented or replaced by immunotherapies, targeted drugs, and cellular therapies like CAR-T. Meanwhile, understanding the interplay of genetic predisposition and lifestyle factors enables more effective prevention strategies. As research continues to advance, through nanotechnology, AI, and personalized medicine, the promise of more effective, less toxic, and ultimately curative treatments becomes increasingly tangible. Continued investment in interdisciplinary research and equitable access will be key to translating these scientific breakthroughs into global cancer control. Dr. Siddhartha Mukherjee, oncologist and author of The Emperor of All Maladies, highlights “Cancer begins and ends with people. In the midst of scientific abstraction, it is sometimes possible to forget this one basic fact.” This is an important reflection and reminder of the human aspect behind the scientific endeavours in cancer treatment. In research, we must keep people, their quality over quantity of life, on the forefront of our minds.