Meditations of an oncology geek

Archive for July, 2014

The Epic Window: Circulating Tumor Cells and the Liquid Biopsy

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14 July 2014

Dear Friends and Family,

I’d like to offer a life-update style post (I’ve been a bit off the radar, sorry!). In the span of the last 90 days the following events happened:

1) I defended my PhD
2) Job applications and interviews
3) I began work at Epic Sciences

The short version is that, after a tumultuous last several months (years?) of my PhD, and the job interview process, I have found myself in a high-energy environment surrounded by diversely talented, innovative, genuinely cool, down to earth people all working together to change the face of oncology. I guess you could say I’m a little excited.

Image: a circulating tumor cell (red) from a profile on Epic Sciences in Discover Blogs

To illustrate challenges in oncology, a quote came to mind from the Emperor of All Maladies:

Specificity refers to the ability of any medicine to discriminate between its intended target and its host. Killing a cancer cell in a test tube is not a particularly difficult task: the chemical world is packed with malevolent poisons that, even in infinitesimal quantities, can dispatch a cancer cell within minutes. The trouble lies in finding a selective poison—a drug that will kill cancer without annihilating the patient. Systemic therapy without specificity is an indiscriminate bomb. For an anticancer poison to become a useful drug, Meyer knew, it needed to be a fantastically nimble knife: sharp enough to kill cancer yet selective enough to spare the patient. – Siddhartha Mukherjee

There has been a wave of new anti-cancer therapies approved by the FDA in the last 5 years, many of which have been touted as ushering in the era of precision medicine. These therapies exploit small molecular discrepancies between cancer cells and healthy cells. The problem is, not all cancers have all the same vulnerabilities and the landscape is incredibly diverse, so much so that leading personalized oncology proponents like Dr. Razelle Kurzrock of UCSD refer to use the metaphor of an individual patient’s cancer molecular profile being as unique as snowflakes, and the correct combination of therapies for every patient might be equally unique.

These precision therapies need informed molecular roadmaps, so patients can receive therap(ies) most suited to them. Currently, this requires tissue samples for requisite molecular analyses. However, tissue biopsies are highly invasive to patients, and longitudinal sampling of how an individual patient’s cancer evolves resistance is nearly impossible with current technology.

The process by which the seeds of tumors establish into metastatic niches (i.e. what causes 90% of mortality from solid tumors) involves transit through the blood, which offers an opportunity for molecular characterization of these cells through a routine blood draw. For years I’ve been very interested in this process, so much so that I did a PhD in this area of research!

The last few years have seen an expanded interest in these circulating tumor cells (CTC’s), as new technologies have emerged to capture and analyze them. This is no easy task; it is literally akin to finding one in one *billion* cells in the blood. About a year ago I became aware of the CTC detecting technology of Epic Sciences. To make a long story short, I recently started working to apply circulating tumor cell (CTC) detection and characterization technology for use in guiding oncology clinical trials.

Image: The Scientist recently produced an overview of CTC detection technologies featuring Epic Sciences

As I alluded to before, tissue sampling of tumors in a cancer patient is highly invasive. No one likes being cut up or prodded, probably just slightly less so than having to get an MRI or PET scan. All of the aforementioned require a trip to a hospital, and a lot of the patient’s and health professionals’ valuable time. Advanced cancer patients might also be too sick for these means of examining their cancer, hindering decisions about what therapies to give (or not to give) or what other measures would be most ethical and humane for the patient and their family.

Blood draws, on the other hand, are minimally invasive, and can be performed even at a local clinic. Blood draws can also be performed frequently; it would be unthinkable to perform a tissue biopsy or a PET scan on a cancer patient twice a month!

While the mere presence of circulating tumor cells gives clues to the stage and progression of a patient’s cancer, the real value is in the molecular and genetic characterization of CTC’s. An immensely unmet need in oncology diagnostics and therapy is a means to confront the intratumor heterogeneity that exists within an individual patient’s disease. A patient’s tumor(s) can be very genetically diverse in both location and time and it’s powerful (and in my opinion pragmatic) to have clues about the cancer cells that can cause the most harm to the patient: the ones that make their way into the blood.

Molecular characterization of CTC’s is a fantastic companion to targeted anti-cancer therapies, and I am thrilled to work as part of a team developing the “Liquid Biopsy” for oncology. I have no reservations saying that I am genuinely excited to get out of bed every morning, and I consider myself a very fortunate man to be able to pursue my passions.

If you have read this far I thank you, dear reader. More (meditations) to come!

Ryon

Written by Ryon

July 14th, 2014 at 6:51 am

Posted in Science Blog