Addressing cancer with a positive outcome is one of the biggest challenges for oncologists, onco-scientists and mankind in general. Treatment strategies are continuously being developed and implemented with marginal benefits. Gastrointestinal (GI) malignancies are of major concern as diet plays a vital role. There are conflicting research data as to what is the best possible diet to delay or altogether avoid GI cancers. Compounding it even further are the social media claims of the benefits to various diet systems and weight loss regimens. Although awareness among general population is at its peak, we are still unable to conquer the increasing rate of new incidences. There are numerous theories as to how the twentieth century chemical revolution has plagued our society with development of non-biodegradable chemicals in form of fertilizers, preservatives and drugs to name a few. The situation is grim with very little hints on how to eliminate such exposure. Thus the disease has to be encountered with different strategies having equal emphasis on both prevention and cure.

Gastrointestinal malignancies are somewhat different from the cancers of other organs like lungs, breast or skin, as it includes an array of organs like the stomach, intestine, rectum along with accessory organs like liver, gall bladder and pancreas. Clinicians specializing in GI malignancies often have to be better trained in organ sub-specialties to deliver the best possible treatment.

As our knowledge regarding genetics and epigenetic characteristics of cancer keeps expanding, we appreciate it as a disease of heterogeneity. Cancer seldom has etiological similarities between two patients or even between different stages of one particular patient which poses serious therapeutic challenges. It is a constant struggle to make the correct and appropriate treatment decisions.

Scientists and clinicians have now begun to appreciate the critical role played by the gut microbiota and the immune stimulation that it provides. The fact that our immune system can successfully handle numerous diseases with its immune gene repertoire have recently gathered tremendous attention. Immune activation happens from within when our system encounters internal and external non-self-molecules. Certain external stimulants can enhance and strengthen the process. The commensal gut microbiota is one such effective agent. It is now accepted that an individual with a strong immune system has reduced chances of developing cancer. We have nicely illustrated the fact by discussing the elimination, equilibrium and escape phases of cancer in the review. Being a clonal disease escape of one single transformed cell can be sufficient to significantly reduce the life expectancy of an individual.

It is long said “we are what we eat.” We now know that “what we eat” determines our gut microbiota and our individual immune strength. It is also appreciated that the best way a heterogeneous disease like cancer can be handled is by boosting our immune power. Many laboratories are working hard to understand how our immune system can be activated and the armamentum it requires to win the battle. Finally, what can be provided from outside to augment the process?

Although our immune system is very efficient in processing bio molecules be it intact or altered, it is inefficient in handling non-biological molecules. The processing is slow, and elimination is harsh deeply impacting the well being of the system. Unfortunately, with modernization our interactions with such non-bio molecules are increasing and so are the number of newly diagnosed incidences.

We in our laboratory focus on colorectal cancer and are involved in both translational and clinical research. Laboratory meetings and journal club discussions are often prolonged dissecting the pros and the cons of various approved therapies, with suggestions as to how we can modify or augment some of the established treatment strategies to enhance immune stimulation/activation. We work with biologics like monoclonal antibodies and viruses and often seek the understanding of the detailed molecular mechanism involved in such processes. So as to enrich our knowledge and compile all the recently implemented immunotherapeutic approaches in GI cancers, we endeavored in writing this review article. It now serves as our own quick reference as we strategize our experiments, techniques and approaches in pursuit to find a cure.