For Patients

The RAS gene is a common oncogene, or a gene that has been shown to cause cancer when it mutates (or changes). The RAS gene makes a protein called RAS that helps control cell growth and survival. These proteins act like a switch turning ON and OFF in response to signals from the body. In healthy cells, the RAS protein is usually in the OFF position [RAS(OFF)]; it only switches ON [RAS(ON)] when cells need to grow and divide. There are different types of RAS proteins, including KRAS, HRAS, and NRAS. These proteins work in similar ways, so they are often referred to as RAS.

A mutation is a change in a gene’s DNA sequence. These types of changes can happen for a variety of reasons. For example, some mutations are passed down from parent to child while other mutations may be caused by environmental factors, such as exposure to chemicals.

A mutation or change in the RAS gene occurs when there is a change in the DNA sequence specific to the RAS gene. When a mutation occurs in the RAS gene, it can cause the RAS protein to stay switched ON, leading to cell growth that is out of control, which, in some cases, causes cancer. Once a RAS gene mutation causes a tumor to form, the tumor depends on signals from the mutated RAS protein to keep growing. This is sometimes called a RAS‑addicted tumor.

RAS gene mutations are present in up to one-third (or about 3 out of every 10 people) of all human cancers. Some cancers rely on RAS mutations more than others. For example, approximately 92% of patients (or about 9 out of every 10) with pancreatic ductal adenocarcinoma (PDAC) have tumors carrying a RAS mutation; in non-small cell lung cancer (NSCLC), KRAS mutations are the most common genetic changes found in approximately 35% of cases (or about 3.5 out of every 10); and in colorectal cancer (CRC), KRAS mutations are present in about 50% of all cases (or about 5 out of every 10).

A biomarker is a biological marker that helps doctors identify or monitor a condition. Biomarkers can be found in blood, other bodily fluids, or tissue samples (such as a tumor). For some cancers, the presence of a gene mutation, such as a mutated RAS gene, may be used as a biomarker to help guide treatment decisions.

A clinical trial is a research study that determines how well an investigational treatment works against an illness and how safe it is. These studies are conducted by doctors and researchers and follow strict guidelines approved by regulatory agencies to ensure the safety of participants. Clinical trials rely on volunteers to help advance medical knowledge and improve health outcomes.

Each clinical trial has criteria to determine if a person would qualify based on factors such as age, medical condition, health status, and medical history. Some trials are for patient volunteers with a specific condition, while others are for healthy volunteers to improve medical understanding of a specific condition. A doctor and research staff will screen the patient to decide whether they meet the clinical trial eligibility criteria. Participation is always voluntary and based on informed consent to ensure understanding of the trial before starting.

There are 4 phases of clinical trials, each designed to determine how well an investigational treatment works and how safe it is before the treatment can be available to the public.

• Phase 1: a new drug is investigated in a small group of patients (20-80) to determine the safety, adverse effects, and best dose of the medication to be used in future trials.
• Phase 2: if the investigational drug is determined to be safe, treatment is expanded to a larger group of patients (100-300) to look for any additional safety concerns and start the initial investigation into efficacy, or if the drug works well to treat patients with a certain disease.
• Phase 3: the investigational drug is used to treat an even larger number of patients (100s-1000s) to further look at the safety and efficacy of the drug. In Phase 3 trials, the investigational drug is generally compared with placebo or existing treatments known as standard of care. It is generally after this phase when a governing group, such as the FDA, will decide if the drug should be available to the public.
• Phase 4: after the treatment is approved, it is monitored in an even wider population over an extended period of time to understand its long-term effects and safety.

The patient can search for a clinical trial on websites like ClinicalTrials.gov or an advocacy group (an organization that supports patients with your type of cancer) website. If patients are interested in a clinical trial, they start by talking to their doctor. Their doctor can help the patient understand if a trial is right for them and guide them through the process.

Informed consent is the process by which the clinical trial team explains the study to the patient before they make the final decision to participate in it. The information includes the trial’s purpose, process, and potential risks and benefits the patient may face by participating. The trial team also allows the patient to ask any questions they may have; these could be related to the treatment, eligibility requirements, or testing. The trial team will review the patient’s rights and how they are protected throughout the trial, even if the patient decides to leave the trial early. After this discussion, the patient will receive an informed consent form that summarizes all the key details. Signing this form confirms that the patient understands the study and agrees to volunteer for the trial.

Patients should speak to their doctor if they are interested in a clinical trial. The doctor can help them determine if a trial is available and if they meet the eligibility criteria. If initial eligibility is determined, the doctor will refer the patient to a clinical trial site and guide them through the screening process for the trial.

Yes, a participant can leave a clinical trial at any time for any reason as stated on their informed consent form. However, it is important for the patient to let the clinical trial doctor know why they have decided to leave the trial, as the information may need to be included in the final data analysis. The trial physician will also help the patient move off the study treatment appropriately in order to avoid unnecessary adverse events.