Can You Improve Your Response to Certain Immunotherapy Drugs?


Written by Emma Shtivelman, PhD

Cancer treatments that use a strategy called immune checkpoint blockade (ICB) have entered clinical practice in a big way, with six drugs now approved by the U.S. Food and Drug Administration (FDA) for a variety of cancers. These drugs release “brakes” on the immune system, boosting its ability to kill cancer cells. Specifically, they target the proteins PD-1 or CTLA-4, which are found on the immune system’s T cells, or the protein PD-L1 on tumor and other cells. Patients’ response rates, however, have been lower than hoped for in most cancers.

Much research and discussion has focused on analysis of particular features in tumors themselves that predict how they might respond to ICB. However, because ICB drugs act on immune system proteins, it is clear that each patient’s immune system is a major player in shaping response to treatment, and that certain tumor-independent features are at play. Here’s what we know about seven factors besides tumors themselves that may predict a patient’s response to ICB: Continue reading…

Predicting If an Immune Checkpoint Drug Will Work


Written by Emma Shtivelman, PhD

Drugs that activate the immune system to attack cancer in a process known as immune checkpoint blockade (ICB) are a focus of intense investigation. A number of them are already approved by the U.S. Food and Drug Administration (FDA) for various cancers; namely, the anti-CTLA4 antibody ipilimumab (Yervoy), two anti-PD-1 antibodies: pembrolizumab (Keytruda) and nivolumab (Opdivo), and three anti-PD-L1 drugs: atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These ICB drugs have the potential to induce durable cancer regressions, but the majority of cancer patients just do not respond to them at all.

Biomarkers, signature molecules in the blood or other tissue, can sometimes be used to predict a patient’s response to a given treatment. But no reliable biomarkers exist for ICB, and this is a serious concern. Patients who may really benefit from ICB could be overlooked, and patients who are not likely to respond may receive useless (and very expensive) ICB treatment.

Most potential response predictors that have already been identified are not yet useful for one or all of the following reasons: they are not extensively validated, their significance is still uncertain and may differ from one cancer (or even one patient) to another, or they are technically challenging for routine use. These markers are addressed below. Continue reading…

A Gut Feeling: Bacteria in Your Gut May Affect Cancer Treatment


Written by Emma Shtivelman, PhD

The human gut contains hundreds of species bacteria, which are known to contribute to various bodily functions (such as digestion, of course!) but they also shape our immune system. Now, recent research has revealed how our microbiomes (the abundant bacteria living in our bodies) may affect the efficacy of immune checkpoint blockade (ICB) in cancer treatment.

How it started: about two years ago, an American group of scientists led by Thomas Gajewski of the University of Chicago noticed that melanoma (and some other cancers’) growth in mice was influenced heavily by the type of bacteria found in the mouse gut. They worked with mice purchased from two different vendors, and realized that mice from one vendor had consistently slower-growing tumors. Bifidobacterium bacteria present in the mouse gut were pinpointed to be the culprit, because transfer of Bifidobacterium to mice that did not have it was able to slow down melanoma growth. Treatment with an immune anti-PD-L1 drug was effective in mice that had the bacteria, but not in mice lacking it. Continue reading…

Testing for Tumor Mutations: Liquid Biopsy Versus Traditional Biopsy


Written by Emma Shtivelman, PhD

Liquid biopsies, virtually unknown even a year or two ago, are becoming common tools in precision diagnostics for cancer. Here, I will try to explain some of the more important differences between liquid and “traditional” tumor biopsies.

Biopsies of solid tumors (e.g., lung, breast, or brain tumors) involve surgically removing a small part of a tumor and sending it to pathology lab. In the last few years, doctors have also started to send some tumor samples to special service labs that analyze tumor DNA for the presence of cancer-related mutations.

By definition, regular biopsies can be intrusive and are sometimes associated with side effects, such as bleeding or infection. However, they provide some really essential information; i.e., the histology and grade of the tumor and other tumor characteristics necessary to determine the best choice of treatment. For lung cancer, for example, a biopsy determines the type of tumor—adenocarcinoma, squamous cancer, small-cell lung cancer, or another, less common type. For breast cancer, a routine test will determine if the tumor expresses estrogen, progesterone receptors, and a protein called HER2. These tests are critically important in guiding treatment choices. If mutational analysis of cancer-related genes is also performed (which doesn’t always happen, unfortunately), it may guide treatment with targeted drugs. Continue reading…

Clinical Trial Versus Standard Protocol: Why and How to Enroll in a Trial


Written by Emma Shtivelman, PhD

My job at Cancer Commons is to help cancer patients better understand and make decisions about their treatment. Through our Ask Cancer Commons service, I also strive to inform patients about new drugs in trials that they can discuss with their oncologists. Sometimes, I explain the rationale behind a patient’s current or upcoming treatment, and sometimes I try to convince patients to actually get treated, rather than hope that a vegetarian diet and herbal supplements will cure their metastatic disease. Continue reading…

A neuroendocrine tumor of the small intestine. Credit: Nephron

New Treatments for Gastrointestinal Neuroendocrine Tumors


Written by Emma Shtivelman, PhD

Neuroendocrine tumors of the digestive system (GI-NETs) can arise in different parts of the digestive tract. GI-NETs originating in the ileum, duodenum, and appendix are known as midgut NETs, and tumors of the stomach, colon, and rectum are non-midgut NETs. Many of these tumors are functional; that is, they produce a variety of hormonal substances that cause serious, debilitating symptoms. Continue reading…

Super Patient: Diane Milne Gives Other Cancer Patients the Tools that Helped Her Survive


Written by Robin Meadows

June 14, 2014 started out like any other day for Diane Milne. But then, just before the two-hour Zumba exercise class she took almost every morning, she suddenly couldn’t breathe. “I had an overwhelming sense of doom,” recalls Diane, a 68-year-old retired nurse. “I was home alone and I thought I was going to die.” Continue reading…

Drugs that target cancer stem cells (yellow) could help prevent tumor relapse. Credit: Peter Znamenskiy

Cancer Stem Cells and How to Get Rid of Them


Written by Emma Shtivelman, PhD

If you have not yet heard of cancer stem cells (CSCs), often considered to be the real culprits in cancer, it is about time you do. CSCs are stem cells found in tumors. Drugs that target them are showing promise in clinical trials. More on that later; first, let’s introduce the concept of stem cells:

All normal tissues in our bodies develop from a small number of very special cells known as stem cells. Stem cells can divide a seemingly unlimited number of times. Continue reading…