Resistant Cancer Cell Line (RCCL) Collection

About the RCCL

Welcome to the Resistant Cancer Cell Line (RCCL) Collection: An extensive collection of studying acquired drug resistance in drug-adapted cancer cell lines.

We have established the Resistant Cancer Cell Line (RCCL) collection to study acquired drug resistance in different types of cancer. This unique collection comprises over 3000 cancer cell lines representing acquired resistance across 18 cancer types and includes cell lines adapted to more than 100 cytotoxic anti-cancer drugs. The full list of cell lines in the RCCL Collection is available here.

Explore Cancer Cell Lines

Background - Cancer Cell Lines

Earle et al. generated the first mammalian cell lines in 1943 from the subcutaneous tissue of a C3H mouse strain, and many cell lines used today were produced from the L strain in those early investigations. HeLa, the first human cell line, was established several years later, and since then there has been an increase in the use of human and mouse cell lines as models for cell biology, genetics, diseases such as cancer, virus production and vaccine development, and as tools for synthesising recombinant proteins for use as therapeutics.

Cancer cell lines are cell cultures derived from cancerous tissues that have been adapted to grow and proliferate indefinitely under laboratory conditions. These cell lines serve as valuable tools in cancer research, allowing scientists to study the biology of cancer, test potential therapies, and investigate the mechanisms underlying cancer development and progression. However, researchers continue to work towards developing more representative and clinically relevant models for cancer research, such as patient-derived xenografts (PDX) and organoids.

Acquired drug resistance in Cancer

Acquired drug resistance poses a major challenge in cancer treatment. It refers to the phenomenon whereby cancer cells, initially responsive to a particular drug or combination of drugs, gradually develop resistance, leading to therapy failure and disease progression. This resistance can arise during or after treatment and may result in cancer recurrence or the development of metastatic disease. The emergence of acquired drug resistance is a key factor underlying the limited success of many anti-cancer therapies. While many cancers initially respond well to drug treatment, resistant cancer cells often emerge over time, ultimately causing therapy failure and patient mortality. Understanding this process is crucial for developing improved methods to detect resistance as it occurs and for identifying appropriate subsequent therapies.

Studies have shown that the mechanisms driving acquired resistance can differ substantially from those underlying intrinsic resistance. Consequently, pre-clinical model systems of acquired drug resistance are essential to bridge this gap. Such pre-clinical models enable researchers to:

• Monitor processes at the systems level in cancer cell populations in response to therapy over time, which is limited in the clinical setting due to intra-tumour heterogeneity.
• Investigate a wide range of cancer treatments, which is clinically constrained by patient numbers and the ethical requirement to provide each patient with the best available therapy.
• Conduct extensive functional studies, including the comparative testing of different therapy regimens in a given cancer population, whereas clinically each individual patient can only undergo treatment once.

Using drug adapted cell lines as a model for acquired drug resistance in cancer

Drug-adapted cell lines, also known as drug-resistant cell lines, are cancer cell lines that have been deliberately exposed to gradually increasing concentrations of a specific drug or combination of drugs over time to induce resistance. These cell lines provide valuable models for studying acquired drug resistance in cancer. Researchers use drug-adapted cell lines to investigate the underlying mechanisms of resistance, evaluate potential therapeutic strategies, and develop new drugs to overcome resistance.

Cancer cell lines are a leading preclinical model system. They are easy to handle and manipulate, and they allow the generation of a large number of individual models needed to capture the complexity of resistance formation. Major resistance mechanisms have been identified in drug-adapted cell lines, such as the ATP-binding cassette (ABC) transporters ABCB1 (also known as P-glycoprotein or MDR1) and ABCC1 (also known as MRP1). Furthermore, drug-adapted cancer cell lines have been successfully used by multiple research groups to identify and investigate clinically relevant mechanisms of acquired resistance to both targeted and cytotoxic anti-cancer drugs.

Using drug-adapted cancer cell lines derived from the RCCL collection, we have demonstrated that resistance to MDM2 inhibitors arises through the formation of de novo p53 mutations, a finding that has recently been confirmed in clinical settings. Additionally, a screen of a panel of drug-adapted urothelial cancer cell lines identified the vinca alkaloids vinblastine and vinflunine—the approved second-line therapy for metastatic urothelial cancer—as the most effective compounds. Most recently, we have shown that high SAMHD1 expression confers resistance in cytarabine-adapted acute myeloid leukaemia cell lines. Based on this discovery, SAMHD1 has been established as both a biomarker for cytarabine response in the clinic and a novel therapeutic target in acute myeloid leukaemia.

Establishing drug adapted cancer cell lines in the RCCL Collection

In the drug adaptation process, a drug-sensitive cell line is exposed to a drug, typically through a process of dose escalation. This involves initially growing the cells in a low concentration of the drug and gradually increasing the dose over time, as illustrated in the figure above. For some cell lines, this process can take more than a year.

Once the cells have developed resistance to the drug—typically defined as an IC50 more than two-fold higher than that of the parental cell line—they can serve as a model of acquired drug resistance in cancer. These cell lines can then be used to investigate the mechanisms underlying drug resistance, assess sensitivity to other drugs, and identify biomarkers of acquired resistance.

Summary of Features available on the RCCL

1. Cell lines information

The RCCL gives you detailed information about the cell lines and thier drug-adapted sublines (for detailed view, please go to Cell lines page), thier drug sensitivity data (for detailed view, please go to Search page), and thier genome sequencing data (for detailed view, please go to Cell lines page). Drug sensitivity data is information about how well a drug works against a particular disease. It was created by measuring the drug's effect on cancer cell lines and their drug-adapted sublines and documenting the results, including the drug's concentration required to kill a specific percentage of cells (e.g., IC50). Genome sequencing data from cancer cell lines are the genetic blueprints of cancer cells, identified by examining their DNA or RNA sequences to find mutations, structural abnormalities, and other modifications that cause cancer.

2. Dose Response Curves

The RCCL provides detailed response curves of the drug-adapted cell lines hosted by it. A dose response curve is a fundamental tool used to evaluate the sensitivity of cells to a drug and to identify the development of drug resistance. By exposing cells to a range of concentrations of a compound and measuring a biological response, such as cell viability or proliferation, researchers can plot the effect of the drug against its concentration to generate a sigmoidal curve. The midpoint of this curve, known as the half-maximal inhibitory concentration (IC50), indicates the drug concentration required to reduce cell viability by 50%. Comparing the IC50 values of parental and adapted cell lines allows for the quantification of acquired resistance, with an increase in IC50 in the adapted cells indicating reduced drug sensitivity. Dose–response curves also provide insights into the slope and efficacy of the drug, helping to characterise the extent and mechanism of resistance and to guide the optimisation of treatment strategies.

3. STR Profiles of Drug Adapted Cancer Cell Lines

You can visualise short tandem repeats (STR) profiles of these drug adapted cell lines to understand their authneticity.

STR profiling of drug-adapted cancer cell lines provides valuable insights into the genetic changes that arise in response to drug exposure. Such changes may involve genes associated with drug metabolism, DNA repair, cell cycle regulation, and apoptosis. By comparing the STR profiles of drug-adapted cells with their drug-sensitive counterparts, researchers can identify genetic alterations that are linked to the development of drug resistance.