Cancer remains a leading cause of death worldwide, with the number of cancer-related fatalities estimated to reach 18.2 million by 2050 (1). In 2025, more than two million new cancer cases were diagnosed in the United States, with approximately 600,000 cancer-related deaths reported (1). Currently, the most common cancers include breast cancer, prostate cancer, and lung and bronchial cancer, although these are not equally abundant in both men and women.
The history of cancer awareness began 250 years ago when, in 1775, a relationship between chimney soot and the incidence of squamous cell carcinoma was first identified. Since then, there have been many notable advances in the understanding and treatment of this disease, including the breakthroughs listed in Table 1.
| Year | Milestone |
|---|---|
| 1882 | William Halsted performs the first radical mastectomy to treat breast cancer |
| 1899 | The First Use of Radiation Therapy to Cure Cancer |
| 1902 | Theodor Boveri proposes that tumors arise from single cells that have experienced chromosome damage causing uncontrollable cell division. |
| 1937 | The National Cancer Institute (NCI) is established. |
| 1949 | FDA approves mechlorethamine for the treatment of cancer. |
| 1958 | NCI researchers demonstrate that combination chemotherapy with the certain drugs can induce partial and complete remissions and prolong survival in children and adults with acute leukemia. |
| 1964 | For the first time, a virus, the Epstein-Barr virus is linked to a human cancer. |
| 1984 | HER2 Gene Discovered |
| 1997 | FDA approves rituximab, the first monoclonal antibody approved for use in cancer therapy. |
| 2006 | FDA approves use of Gardasil, the first vaccine approved to prevent cervical cancer. |
| 2012 | Trial confirms effectiveness of early colorectal screening in reducing incidence and mortality related to colorectal cancer. |
| 2013 | FDA approves ado-trastuzumab emtansine, an antibody-drug conjugate, for the treatment of breast cancer patients. |
| 2017 | FDA approves tisagenlecleucel, a CAR-T cell therapy to treat acute lymphoblastic leukemia |
| 2020 | Scanning for tumor related DNA in blood provides the first liquid biopsy diagnostic tool for solid tumors. |
| 2024 | FDA approves two T cell–based therapies to treat cancer: tumor infiltrating lymphocytes for advanced melanoma and T-cell receptor therapy for metastatic synovial sarcoma. |
Cancer treatments throughout the decades have mirrored the technological advances available at the time. At the end of the 19th century, radiation therapy began to be introduced as a treatment following the identification of high energy electromagnetic radiation (X-rays). Several decades later, the serendipitous discovery (during WWII) that mustard gas, and its related nitrogen mustard derivatives, resulted in a decrease in lymphomas, opened the way to chemical treatments for cancer.
The use of these types of treatment was effective but not specifically targeted to cancer cells and thus resulted in toxic and immunosuppressive effects through destruction of the patient’s bone marrow. This necessitated the use of additional treatments or procedures to counter these deleterious side-effects.
Developments in immunology throughout the 20th century, along with an increased understanding of how the immune system interacts with cancers, led to the development of monoclonal antibody-based treatments along with other cell-based treatment regimes.
Continued investigations into the genetic and protein-based profiles of cancers have led to a greater understanding of cancer and cancer subtypes at the mechanistic level. This knowledge, combined with modern genetic engineering techniques, has opened the door to novel and imaginative treatments that are more specifically targeted to cancer than previously achievable.
The ability to provide focused cancer treatment has clear implications for the general health of the patient who is far less compromised as a result of a targeted treatment regime.
One manifestation of focused treatment is the use of monoclonal antibodies to act as targeting mechanisms for drug delivery, leading to the development of the class of products known as antibody drug conjugates (ADCs). This approach allows cytotoxic drugs, which would otherwise produce adverse reactions in patients, to be used more effectively for cancer treatment.
ADCs have proven effective treatments for different cancer types with the FDA, EMA, and other countries’ regulatory bodies approving their use. Globally, 19 ADCs have been approved up to mid-2025 (2). Some examples are shown in Table 2.
| ADC | Therapeutic use(s) |
|---|---|
| Kadcyla | HER2- positive breast cancer |
| Enhertu | HER2-positive breast cancer. Gastric cancer. HER2 mutant non-small cell lung carcinoma |
| Trodelvy | Breast cancer. Urothelial cancer |
| Adcetris | Hodgkin lymphoma. Anaplastic large cell lymphoma |
Building upon the inroads that ADCs have made in cancer treatment, new ADC modalities are currently under investigation that enhance the target binding capabilities of the antibody portion of the ADC. These resulting so-called bispecific and trispecific ADCs are still under development, with currently only one approved bispecific (Blincyto) on the market. These products represent enhancements in terms of cross reactivity with both cancer and immune system effector cells, serving to bring the immune response directly to the cancer.
Increasing insights into the genetics of cancer have opened new avenues for treatment. Understanding the genetic mechanism of action (MOA) of cancers provides a new approach to treatment through cancer disruption at the genetic level rather than a cellular cytotoxic approach. To this end, a fusion of the disciplines of genetic engineering, protein engineering and chemistry is producing antibody-oligonucleotide conjugates with specific and precise targeting and molecular functionality at the precise site of action, to effectively inject genetic material into cancerous cells to disrupt them.
Ongoing development in the area of conjugated therapies is not limited to considerations of the nature of the active drug but also extends to new mechanisms for more precise targeting. This has been at least partially alluded to above, but researchers are exploring beyond the antibody, long perceived as the best targeting mechanism, to other smaller protein or peptide modules encoding only the necessary information for precise target binding, such as nanobodies and peptides. These smaller chemical entities offer enhanced tissue penetration and also potentially make for an easier-to-produce drug.
The analytical chemistry needed to demonstrate correct product manufacture and to assess unwanted reaction by-products present in cancer conjugated therapies must be thorough and as state-of-the art as the chemistries used to produce the drugs themselves. Analytical methods must be able to handle the new and diverse range of products both in the development pipeline and in researcher’s imaginations.
These conjugated products vary in biopolymer species (e.g., proteins, nucleic acids) as well as in the chemical entities that may be used both as drug and linker combinations, or as modifications to any nucleic acid species used in the conjugate to increase nuclease resistance and product half-life or stability.
The use of mass spectrometry as a primary analytical tool in the analysis of this increasing range of cancer-targeting products is of supreme importance for demonstration of product fidelity, with other ancillary techniques adding to the wider range of product knowledge such as aggregation state, higher order structure investigations and charge profile assessments. Armed with these analytical tools, imaginative products can be developed and manufactured safely for more targeted, effective cancer treatment in the future.
Antibody-Drug Conjugates demand precise structural characterization and deep analytical expertise. BioPharmaSpec supports ADC developers with state-of-the-art mass spectrometry, higher-order structure analysis, and regulatory-ready data to accelerate development with confidence.
