More about oncogene cancers.

An oncogene is a mutated gene that has the potential to cause cancer. Before an oncogene becomes mutated, it is called a proto-oncogene, and it plays a role in regulating normal cell division. Cancer can arise when a proto-oncogene is mutated, changing it into an oncogene and causing the cell to divide and multiply uncontrollably. Some oncogenes work like an accelerator pedal in a car, pushing a cell to divide again and again. Others work like a faulty brake in a car parked on a hill, also causing the cell to divide unchecked.

Identifying oncogene-driven lung cancer.

Everyone diagnosed with non-small cell lung cancer – especially lung adenocarcinoma – should have comprehensive biomarker testing done on their tumours to look for oncogenes (or genetic abnormalities) in their lung cancer cells.

Common drivers in lung cancer include:

  • EGFR

  • ALK

  • ROS1

  • RET

  • MET

  • KRAS

  • HER2

  • BRAF

  • NTRK

 While hereditary gene mutations (germline mutations) – those which you carry from birth – the mutations which are found via biomarker testing are usually acquired gene mutations (somatic mutations) found only in the cancer cells. While cancer cells can have many mutations, oncogene-driven mutations are the ones that are directly involved in the cancer process. These mutations drive the growth and spread of the cancer. Some, but not all, of the driver mutations are also targetable or have actionable mutations – meaning that they can be targeted with a drug. 

There are targeted therapies are available for most of these alterations. These medications specifically target cancer cells and often have fewer side effects and better quality of life than traditional chemotherapy.

Some facts about a few common oncogene cancers.

EGFR

  • More common in women

  • Also in Asians, particularly East Asian heritage

  • Accounts for roughly 50& of lung cancers in young adults

  • 15% of lung cancers express EGFR

  • More likely in those with little or no smoking history

ALK

  • 50% are diagnosed before age 50

  • Occurs in approx. 5% of all lung cancers.

  • Approximately 30% ALK+ lung cancer patients diagnosed under age 40

  • Occurs mainly in lung cancer; can originate elsewhere - like the brain, bowel and breast

  • No known risk factors

RET

  • Occurs in 2% of non-small cell lung cancers

  • Average age <60 and no risk factors

  • 10-20% of papillary thyroid cancers

  • 1-2% of other cancers, including pancreatic, colorectal, bladder and breast

KRAS

  • KRAS is the most common biomarker associated with lung, colorectal, pancreatic plus other cancers. 

  • KRAS accounts for around 25% of lung adenocarcinomas

  • Two most common KRAS 
    mutations in NSCLC, G12C (∼40%) and G12V

ROS1

  • Approximately 2% of non-small cell lung cancers

  • Similar frequency in other cancers including brain, blood vessels, skin, bile ducts, liver, pancreas and ovaries

  • No known risk factor or behaviours

  • Younger than the average

  • Likely from a random DNA copy mistake

NTRK

  • Occurs in rare tumours, like secretory breast and salivary gland cancers (90%), some childhood sarcomas and childhood thyroid cancers (26%)

  • Also happen in a small percentage of more common tumours, including lung, thyroid and colon cancer (1-5%)

MET

There are 4 major categories of MET protein alterations:

  • Mutation

  • Amplification

  • Over expression

  • Fusion

Primary versus acquired MET alterations.

When lung cancer is first diagnosed, there may be only a single genetic alteration. This is the primary genetic alteration. However, a genetic alteration can also be acquired as a resistance mechanism to treatment. For example, a person with a primary alteration of EGFR or ALK, who has been on a drug for that alteration, may also later acquire a MET alteration. They will then have two genetic alterations which may be treated in combination.