Antibody-Drug Conjugates (ADCs): A Promising Treatment for Lung Cancer

Author: Renee Botello, MSc, Navigator, Treatment and Trials, GO2 for Lung Cancer

With decades of research and advances in precision medicine, scientists continue to broaden the treatment standards and options for patients with non-small cell lung cancer (NSCLC). By developing new ways, strategies, and innovative research techniques, this rapid development leads to a future direction of transformative potential for patients with limited treatment options. Precision medicine acknowledges that each cancer is unique, and as such, the treatment approach should factor in the patient’s health history, genetic makeup, and lifestyle. These innovative models can transform cancer treatment into a more promising, efficient, and person-centered approach by tailoring treatment to target specific biomarkers.

Antibody-Drug Conjugates (ADCs): What they are and how do they work?

A fast-growing class of precision oncology drugs, antibody-drug conjugates (ADCs) demonstrate the importance and innovation of precision medicine for lung cancer treatment. ADCs are an expanding targeted therapy option for NSCLC that combine the selectivity of monoclonal antibodies (which identify a protein or receptor commonly observed in cancer cells) and the response of chemotherapeutic drugs to deliver a high dose of the cancer-killing drug that destroys rapidly dividing cells.

ADCs are comprised of 3 main components 1) an antibody, 2) a linker, and 3) a cancer-killing drug.

1. Antibodies serve separate roles, but their ability to identify certain receptors or cells in the cancer are what allow the ADCs to bind to targeted cells. In this case, antibodies can help custom design the interaction with a specific mutation or genetic alteration, as determined by a biomarker test result.
2. A linker does what it states: it “links” the antibody and the cancer-killing drug. In ADCs, the linker was designed for stability when traveling across the bloodstream, ensuring that the cancer-killing drug is not released before it reaches the target cells and limits the exposure of the drug to the otherwise healthy cells.
3. The cancer-killing drug is a potent chemotherapy drug that kills cancer cells, which may stop the spreading and dividing of the tumor.

When the ADCs reach and bind to the target cell (like the cancer cell), the linker releases the cancer-killing drug. As observed with chemotherapy, once the cells interact with the drug, this leads to cell death, which can stop the cancer from spreading or growing. As ADCs are designed to selectively bind and attack cancer cells, this may improve the response to treatment and limit the drug’s exposure to healthy cells.

How do ADCs differ from other forms of treatment?

Traditional cancer treatments, such as chemotherapy or radiation, work by acting against the rapidly dividing cells in the body in a one-size-fits-all approach. Although widely used in the cancer treatment setting, these types of therapy also damage the normal cells in the body, which contribute to the systemic toxicity, or side effects. The concept of targeted drug delivery such as ADCs allows for the chemotherapeutic drug to attack only the cancer cells without exposing the drug to the normal cells. Like tyrosine kinase inhibitors for EGFR-positive NSCLC (such as Tagrisso (osimertinib)), targeting the cancer’s unique features limits the exposure of normal cells to cancer drugs, which may increase the efficacy of the treatment outcome.

ADCs and biomarker testing

ADCs have shown promising pre-clinical results in lung cancer, particularly in patients with a positive or specific biomarker alteration. Because ADCs are designed to target specific receptors or proteins in the cell through their antibody component, having a comprehensive biomarker test allows patients and their physicians to understand the targeted approach and the possibility of increased efficacy in the treatment choice. Currently, ADC targets include HER2, HER3, TROP-2, EGFR mutations, and other alterations. Although some of the currently established mutations are also recognized biomarkers for other cancers (such as HER2 in breast cancer), ADC development and study in lung cancer highlights the need to define more comprehensive biomarker testing across different tumor types.

It is important to note that to date, ADC research continues to evaluate its benefits and limitations, alone or in combination with other types of treatment, including radiation, chemotherapy, or immunotherapy. Furthermore, its development and study of response to specific biomarkers will allow for a more in-depth understanding of the availability of this treatment, its mechanism of resistance, and its next steps in precision medicine.