Molecular Testing & Targeted Therapies


Who Should Be Tested? 

Many patients are eligible for molecular testing including most patients with adenocarcinoma.  If your tumor hasn't been tested or are not sure if it has been tested, talk with your doctor to find out if you are eligible.

When Should You Get Tested?

Your tumor may have been tested with your initial biopsy. However, if not enough tissue was collected molecular testing can be done at any time.

Where Can You Get Tested?

Most major medical centers often offer molecular testing. Talk to your doctor to discuss getting tested.

Cancer is caused by genetic changes, called mutations, which transform a healthy cell into a cell that stops doing its normal job, and instead divides and spreads.  The specific changes present in a particular tumor are defined by molecular markers which can be tested by a variety of methods.  Here’s a breakdown of the most common lung cancer mutations:

(Weiss, Oncologist 2013)


EGFR is present in about 15% of adenocarcinoma.  Guidelines say that any patient with adenocarcinoma should be tested for EGFR, but statistically, the mutation is more common in nonsmokers, women and Asians.  There are three classes of drugs that treat EGFR-mutated lung cancer: 1st generation tyrosine kinase inhibitors, 2nd generation tyrosine kinase inhibitors, and 3rd generation tyrosine kinase inhibitors.  The only FDA approved 1st generation tyrosine kinase inhibitor is erlotinib, which is a daily pill.  Erlotinib controls cancer longer than chemotherapy.  Its major side effects are diarrhea and an acne-like rash.  Gilotrif (afatinib) is the only FDA approved 2nd generation tyrosine inhibitor.  There are many approaches to EGFR mutated lung cancer when it grows through erlotinib or gilotrif.  The most frequent resistance mechanism is T790M; T790M inhibitors such as CO1686 and AZD9291 are in clinical studies; early results are very promising.


EML4/ALK is a rearranged gene that is found in about 4% of adenocarcinoma of the lung.  The development of ALK inhibitors for patients whose cancer is driven by this change is inspiring; it was the fastest time from scientific discovery of target to FDA-approved drug ever. just did a patient forum on everything ALK-related at the Santa Monica Targeted Therapies meeting.  The videos cover basics, xalkori (the first FDA approved drug to treat ALK-driven lung cancer), testing for ALK, heritability, and flare reactions.  They also talk about what to do when crizotinib stops working in videos on scanning for progression, disease progression while on xalkori, repeat biopsies, and next generation ALK inhibitors.  The last subject is particularly important since a new ALK inhibitor, ceritinib (brand name Zykadia), was just approved for patients whose cancer has grown on crizotinib.


ROS1 is another rearranged gene with a lot of biologic similarity to ALK.  It is present in about 4% of adenocarcinoma of the lung and is treatable with the targeted therapy crizotinib (same one as for ALK).


There have been several failed trials of MET inhibitors.  Many academic experts believe that the failure was due to using the wrong lab tests to identify which patients would benefit from MET inhibitors.  In the summer of 2014, the field finally got some positive news on MET and crizotinib is being evaluated in a clinical trial (believe it or not, crizotinib was originally developed as a MET inhibitor, not an ALK or ROS1 inhibitor).


This rare mutation is not yet actionable outside of a clinical trial, but there are trials evaluating BRAF inhibitors with real promise.


kRAS has been known to be mutated in human cancers since about the dawn of the internet, yet we still have no effective kRAS directed therapies.  A lot of things have been tried; some even seem to be active, but as of now, none preferentially for kRAS.  This remains an active are of investigation.

(Information provided by Board Member, Jared Weiss, MD and 

Other Resources:

Lung Cancer Biomarkers Discussion Guide

Lung Cancer Profiles

Don't Guess. Test.

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