More than a year ago, I wrote an introductory post about mutations in KRAS, one of the genes that contributes significantly to cancer cell growth and signalling, at least in many cancers. It's seen in around 20% of lung cancers, almost always in adenocarcinomas and not squamous NSCLC, and it's been implicated as being associated with a low likelihood of response to EGFR inhibitors.

One of my earliest posts when I started OncTalk was on the use of oral inhibitors of the epidermal growth factor receptor (EGFR), one of the growth signals that is often over-active in cancer cells, against advanced bronchioloalveolar carcinoma (BAC), a unique subtype of lung cancer that tends to grow within the lungs, sometimes slowly, and not progress elsewhere.

So I’ve been invited to be on the faculty of a lung cancer conference in Kauai next month (yes, a good gig, but this is the first year that the flights are so expensive that I can’t bring my family to this normally very family-friendly event), and my topic is to argue in a debate about whether molecular testing for EGFR should be routinely used in clinical practice.

Continuing with the analysis of a publication about tarceva (erlotinib) for patients with advanced BAC that I introduced in the last post, we'll turn now to the analysis that Dr. Vince Miller and colleagues did on the biomarkers that might predict more or less clinical benefit with an EGFR inhibitor like tarceva (abstract here).

In a recent issue of the Journal of Clinical Oncology, Dr. Vince Miller and colleagues published the results of an important trial of the EGFR inhibitor tarceva (erlotinib) in the unusual NSCLC subtype bronchioloalveolar carcinoma, or BAC (abstract here). This work was predicated on the observation, also by Dr.

One of the issues we struggle the most with, as oncologists, patients, and families, is how to choose a therapy that won’t make someone feel worse. There are so many things to factor into these decisions: what is the baseline function of the person, what comorbidities (other chronic illnesses) might interact or interfere, what side effects are acceptable or worth the risk, to what degree is the cancer interfering with their functioning and can this be reversed with chemo, and of course what does any individual patient want and expect from chemo?

While the differences in anticipated clinical benefits from EGFR tyrosine kinase inhibitors like tarceva and iressa are well known (summarized in prior post), less well appreciated is the potentially significant differences in results with garden variety standard chemotherapy.

The issue of population-based differences in response to lung cancer treatments was essentially introduced with the EGFR inhibitors, so it’s appropriate to introduce racial differences overall with this work. Mention of more favorable results with EGFR inhibitors iressa and tarceva emerged with the earliest clinical studies and have since become a well established truism. Let’s explore what we know now and how we got here.

Infused throughout the website is a constant recognition that "patients are different", but while we know this intuitively, we're really not moved to a point of individualizing treatment on the basis of this. There are many lines of clinical research that are moving in that direction, and one of the key elements is pharmacogenomics, the study of the genetic underpinnings of the differences among people in response to a medication, both in terms of response and side effects.

In the Q&A forums recently, members Jianming and Neil introduced us to the novel agent XL647, in clinical trials now, but I figured it was worth me collecting more background and providing a more thorough background. XL647 is an oral small molecular that inhibits multiple tyrosine kinases, receptors on cells that trigger cascades of activity in the cells, thereby leading to tumor development and growth.