Microbiome and cancer treatment: Are we ready to apply in clinics?

Abstract

Cancer treatment has been evolving in recent decades from surgery, conventional chemotherapy and radiation therapy to targeted therapies and more recently immunotherapies. Despite significant improvement in the efficacy of treatment with the discovery of novel therapies targeting particular cancer-related gene and proteins and more recently the immune system-modulating biologics, still only patients with specific subtypes of cancer benefit from those targeted therapies and there is room for further improvement of survival outcomes. As failure of cancer treatment is not uncommon in clinical practice, a lot of biomarker studies have been carried out with an aim to identify factors contributing to disease relapse and treatment failure. Gut microbiome is one of the research areas which warrants further investigation of its impact on cancer treatment as microbiota has long been proven to profoundly shape mammalian immunity. As there is increasing evidence showing a strong association between gut microbiota and clinical outcomes of immunotherapy, modulation of intestinal micro-ecological system may be a possible strategy to help improve therapeutic impact of immunotherapy in oncology practice.

Introduction

Cancer is the second leading cause of death worldwide secondary to cardiovascular disease.¹ According to the GLOBOCAN statistics, there were 18.1 million new cancer cases and about 9.6 million death related to cancer in 2018, and the cancer incidence and mortality are anticipated to reach 29.5 million and 16.4 million, respectively.² Despite the increasing disease burden, the rapid evolution of molecular medicine in the past decade have significantly driven paradigm shift of cancer treatment from conventional surgery, traditional chemotherapy and radiation therapy to molecular, biological and more recently immunotherapies.

While immunotherapy has become one of the treatment strategies in fighting against cancer through modulating the immune system of patients to induce anti-tumor effect, it is evident that some patients may experience resistance to the treatment.³ More efforts are therefore required to investigate the underlying drug resistance mechanism as well as identify patients more suitable to be treated by immunotherapy, so as to improve the treatment efficacy.

Cancer precision medicine or personalized medicine is regarded as using therapeutics that are expected to confer benefit to a subset of patients whose cancer displays specific molecular features (most commonly genomic changes and gene or protein expression patterns).⁴ With the increasing understanding of cancer at the molecular level, clinicians can yield more diagnostic and prognostic information of the disease so that treatment could be tailored for a particular group of patients instead of using “one-size-fits-all” approach such as traditional chemotherapy and radiation therapy in treating cancer patients.

In addition to molecular biomarkers of tumor that determine the efficacy of cancer treatment, intestinal microbiota, which play a role in developing innate and acquired immunity of individual, are now considered able to influence the peripheral immune system of patients and subsequently the clinical response to immunotherapy.5, 6, 7, 8 However, little is known about the specific composition of gut microbiome that can induce greater impact to the treatment efficacy and the underlying mechanism to reverse primary or acquired resistance to immunotherapy by modifying the intestinal microecological system.