# Biomarker Testing

Six cards on driver mutations in lung cancer, how next-generation sequencing finds them, how
a matched targeted therapy compares with chemotherapy, and what to ask at diagnosis.

## 1 — The mutation that won't turn off

In lung cancer, the most important biomarkers are called **driver mutations** — genetic
changes that lock a growth signal in the "on" position, telling cells to keep dividing long
after they should stop.

That permanently-on signal is what makes these mutations so specific — and so targetable.
Shutting it off is exactly what targeted drugs are designed to do.

> Most non-small cell lung cancers have at least one driver mutation. NSCLC accounts for
> about 85% of all lung cancers.

*Source: NCCN / NCI.*

## 2 — The usual suspects

These four driver mutations each have FDA-approved targeted therapies — treatment designed
specifically for that mutation.

| Mutation | Frequency in NSCLC | Example targeted therapy |
|---|---|---|
| EGFR | ~15% | Osimertinib |
| ALK | ~5% | Alectinib |
| ROS1 | ~2% | Crizotinib |
| KRAS G12C | ~13% | Sotorasib |

These are among the most common — but there are many more actionable mutations in lung
cancer. That is why comprehensive testing matters.

> **KRAS: the long-undruggable target.** For nearly 40 years after its discovery in 1982,
> KRAS resisted every drug that tried to block it. Sotorasib, approved in 2021, was the
> first to succeed.

*Source: Journal of Thoracic Oncology, 2023.*

## 3 — NGS: one test, many answers

**Next-generation sequencing (NGS)** — also called broad molecular profiling — reads the
tumour's full DNA and screens for every known driver mutation in a single run.

1. **DNA extraction** — a sample from the tumour is collected and DNA is isolated.
2. **Sequencing** — a machine reads every base in the tumour's DNA sequence.
3. **Analysis** — software scans the sequence for hundreds of known mutations.
4. **Report** — results identify exactly which mutations, if any, were found.

One test. A complete picture. If a targetable mutation is present, NGS finds it — and that
finding determines whether a targeted therapy is an option.

*Source: NCCN Guidelines v2024.*

## 4 — Targeted therapy: precision beats power

Traditional chemotherapy attacks all fast-growing cells — cancer and healthy alike. Targeted
therapy is different. It is engineered to block the specific signal the mutation is sending,
and nothing else.

| Treatment | Response rate |
|---|---|
| Unmatched chemotherapy | ~30% |
| EGFR-matched targeted therapy | ~77% |

That precision shows up in the numbers. The 77% response rate applies specifically to EGFR+
patients receiving a matched targeted therapy — an outcome that is not possible without
testing first.

> Response rate measures how many patients saw their tumour shrink or disappear. For
> unmatched chemotherapy it is roughly 30%. For a matched mutation, it can more than double.

*Source: NEJM / ASCO 2020.*

## 5 — From test to treatment

Testing "positive" for a driver mutation is not bad news — it means a drug was likely
designed specifically for that cancer. It is one of the best results a lung cancer patient
can receive.

> If no driver mutation is found, that is still valuable. It helps the oncologist focus on
> other effective options, including immunotherapy — and both answers have value. Testing is
> the only way to find yours.

*Source: NCI / American Lung Association.*

## 6 — Ask at diagnosis

Three questions worth asking:

1. Should I have broad molecular profiling (NGS) at diagnosis?
2. Can we wait for those results before deciding on treatment?
3. How long will results take, and what do they mean for my options?

Testing rates in community oncology remain below 50%. Most patients are never asked — so ask
first.

> NCCN recommends broad molecular profiling for all patients with advanced NSCLC. You have
> the right to ask about it at diagnosis.

*Source: NCCN / Journal of Oncology Practice.*

## Related

- [What Is a Biomarker?](https://nodule.app/biomarker-basics) — the foundations, if the
  concept is new.
- [Terminology library](https://nodule.app/glossary) — definitions for EGFR, ALK, ROS1,
  KRAS, NGS, and targeted therapy.

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*Educational use only · Not a medical device.* This document mirrors the page at
<https://nodule.app/biomarker-testing>.