Cancer: Revolution under way for Cancer Prevention & Treatment, Are we near Cure?

Dr Ravi Gaur , MD Pathology
Founder & Director DRG Path Labs, New Delhi
Chairman Medical Advisory Committee, Unipath Specialty laboratories ltd

Cancer research – and its impact on patient care – has made some significant strides in just the last 15 years. Scientists and doctors firmly believe that we’re on the edge of a brighter era. Today we have more reasons than ever to be hopeful about the future of cancer care and science.

Where was cancer born, how old is cancer, who was the first to record this illness and many more such questions still remains unaddressed. The history of attempts to understand and control cancer is littered with disappointments and false starts. For over thousand years and more, Cancer has been known to medical profession and since then people are knocking at the doors of medical professionals for cure. Unfortunately Cancer succeeds in entering every time, without knocking .There are fewer success in the treatment of disseminated cancer and its usually a matter of watching cancer growing bigger and the patient, progressively smaller. However, in recent years, many significant advances in research and treatment have been made, yet the disease remains a leading cause of death worldwide.

Decades into the declared modern war on cancer, scientists and clinicians are excited by what we are learning. As the research matures further, we are likely to see new treatment options emerge. Scientists are turning cancer treatment from impossible to probably soon into a ‘normalized’ disease. We are probably almost close to cure! Although among those of us, whose lives have been touched by cancer, many feel frustrated by the slow pace of progress in prevention and treatment.

To understand this seeming paradox, we have to consider what has been learned about the biology of cancer and how we are putting this knowledge to use. Viewed in this light, there is tremendous hope for the future, both in decreasing an individual’s lifetime risk of getting cancer and in increasing the success of treating those cancers that do arise. Just as signposts provide information, direction, and guidance, so too cancer biomarkers can better reveal the complex, dynamic, and heterogeneous landscape of malignancies. Such information is critical for creating better cancer diagnostics, prognostics, and therapeutics, but the journey to find just the right biomarker which is very specific, sensitive and has high predictive value, is often a long and winding road. Biomarker discovery and utilization is being explored by means of various methods and technologies. These include characterization of rare circulating cancer cells, the use of multiplexing PCRs to extract information from limited amounts of sample, and even the application of evolutionary biology to detect early cell changes. Scientists are now developing novel cancer diagnostic approaches.

As per an estimate, there are about 600 cancer driver genes; however, drugs have been developed against only a small subset of them.  Just about few years back the technology using conventional genetic platforms was taking several months for full analysis of samples .But now, the availability and affordability of next generation sequencing platforms, the genetic information has improved greatly – meaning researchers and doctors are now better able to get information about a person’s risk for certain cancers as well as what drugs might work best for cancer patients ad that too in a matter of days. As we compile and collect genomic profiles of vast population  , we are likely to get much required information , which will accelerate the pace of cures. Many other advances have occurred in the areas of targeted therapy, immunotherapy, and cancer screening technology. The ultimate goal is get as much molecular information as possible, as quickly as possible, with as little sample as possible.

Majority of people don’t acquire a significantly higher risk of cancer from the genes that they inherit from their parents. Instead, cancer arises as a result of mutations (copying errors) in the inherited genes, as our bodies make new cells to maintain our various organs. Various publications suggest that, these errors are an inevitable consequence of trying to copy three billion bits of information as a cell divides. That may be true, but it doesn’t mean getting cancer is inevitable. As we can appreciate that , the fastest and most extensive rates of cell division occur when we are developing as embryos. Millions to billions of cells are produced each day, yet cancer in newborns is exceedingly rare. In contrast, cell division in each of our tissues slows as we grow older, while the incidence of cancer increases with age.

Why this discrepancy? During pregnancy, both the mother and the placenta protect the developing embryo from environmental exposure. In contrast, we constantly put ourselves in harm’s way as we age. We are exposed to viruses and bacteria that damage our tissues. And it isn’t just invading pathogens that wreak havoc; we do most of the damage ourselves. Through   active & passive smoking, drinking alcohol, environmental pollutants , sun burns, sedentary life styles ,work stress ,obesity, viral infections, etc , we constantly damage our tissues, forcing restorative cell proliferation to occur in a war zone of damage. It is in this inhospitable environment that most cancers arise. We have known for some time that many of these environmental exposures damage DNA, making it harder to copy and resulting in more mutations as cells divide.

Recently, we have found that during regeneration of damaged tissue, the rest of the body pitches in to keep every cell in the damaged tissue alive. Not just the healthy cells, but also the ones that have acquired mutations that render them unfit. Our immune system, which usually detects and destroys cells with excess mutations, is turned off. The body produces growth factors that stimulate the survival of cells with deleterious mutations, our habits keeps on providing triggers and overeating maintains an excess supply of nutrients that compounds the damage. These are scientific facts we didn’t appreciate even a decade ago. But can this information be harnessed into better cancer treatment and prevention? Yes to some extent – don’t smoke,  avoid unnecessary radiation exposure, exercise, avoid stress, meditate ,regulate life style ,eat healthy, use sun protective creams, get vaccinated and much more. It  is now expected very soon that obesity, will surpass tobacco exposure as the No. 1 cause of preventable cancers.

Our knowledge of genesis of cancer is now growing at a very fast pace .We now understand that cancer is initiated primarily in the cells which have the ability to repair our tissues. When a tissue is damaged, so-called progenitor cells expand in number to fill the damaged area, and once that is accomplished, the cells differentiate to form tissue much like the original. Some of the mutations discovered in cancer cells result in the signal to differentiate not being received or acted upon. As a result, progenitor cells keep on reproducing. Treatments that focus on restoring a cell’s ability to differentiate, thus stopping the excessive proliferation, are already being used successfully . These therapies avoid the toxic side effects of traditional chemotherapy and can effectively eliminate cancer cells even when they have spread throughout the body. Why finding cure is taking so long? As we all know that cancer is not one disease, but many. Each tissue has its own unique progenitor cells, and each tissue uses only a subset of the genes we inherit from our parents; each tissue is exposed to environmental insults differently. We are just beginning to understand the interplay of all these factors in the origin of the many forms of cancer. Understanding these issues will ultimately allow us to optimize the treatment approach to each patient’s disease. While we are fairly at a distance from making cancer on the extinction list like, polio etc, it is clear that as our science matures and with the lessons we have learned in the past two decades—we face the future with less fear.

It takes 10-20 years and from the discovery that a new treatment is effective until it is used in clinical practice. It should be, and could be ten -20 days. Researchers are hopeful that the research in the future will be much quicker as animal studies are replaced probably by computer programs.  Computer models will likely mimic the “patient” with their individual “makeup” and indicate which drugs will provide the optimal outcome.  There is a strong possibility (as we are dealing with humans there will always be exceptions) that, the need for time consuming human trials will eventually be replaced with a more real time approach.

Expert Predict that Cancer care will dramatically change over next decade. There is a big hope and doctors are very optimistic about the cure. There are multiple reasons for the hope. Few promising fields that are likely to transform cancer treatment are as under:

Precision Medicine: Till a decade ago, cancer was treated based on the tissue in which it originated. Increasingly, effective cancer therapy is supported by knowing the precise mutations a patient’s tumor has acquired, independent of where in the body the cancer arose. This approach is called precision medicine. Precision medicine is the vision that all people one day will be offered customized care, with treatments that match our genomic profiles and personal histories. Such individualized therapies promise to be more effective and result in fewer side effects than more-traditional ones developed for the average patient. Many people with cancer have gained dramatically improved options with targeted therapies that reverse the effect of specific gene mutations in their tumor cells. Such drugs are not yet available for most cancer patients. But when they can be used — in the right person with the right type of cancer — their benefit can be decisive. Scientists are working relentlessly to deliver on the promise of precision medicine to people with all kinds of cancer. Pathologists are using a  tumor DNA sequencing and other technologies to guide therapy for all patients with advanced disease, regardless of their tumor type.

Some cancer patients are benefiting from ‘targeted therapeutics ‘(drugs that target specific mutations in their cancer cells). Scientists are working hard to make precision medicine a reality for people with all types of cancer. We don’t have many therapies that target cancer-causing mutations, but the results can be dramatic when such drugs are available This new information for sure, will  revolutionize the cancer care.

We are now in the era of precision medicine. Blood based biomarkers will be used routinely to assess a person’s risk for cancer and personalize cancer treatment. Genomic testing to personalize cancer screening will also be routine in clinical practices all over the world through rapid adoption of technology that allows for assessing cancer risk among the population. These advances will lead to a dramatic drop in deaths from preventable cancers.

Immunotherapy: Our immune system is designed to recognize cells with new properties, as when infected with a virus. Our immune system should respond to the mutations building up in a cancer cell . The more mutations there are, the more likely it is that the immune system can recognize and destroy the cancer cells. Immunologists have found that our immune system has a built-in “off switch,” a checkpoint that shuts down an immune response a few weeks after it is initiated. A new and expanding class of cancer drugs  have been developed that have the ability to block this normal shut off switch and thus increase the ability to recognize and destroy cells carrying mutations. In the right situation, “immunotherapy” ( a group of modified T cells)  can have very successful effect .Some patients with widely metastatic cancer have been rendered cancer-free with therapies aimed at increasing the body’s own ability to fight cancer.

Epigenetic Therapy: In the history of medicine, doctors have worked on ways to control cancer by surgery , chemotherapy  and radiation. Can we transform cancer cells back to normal rather than destroying them?. Researchers are gone deep into epigenetic — an intricate system of biochemical adjustments, which cells use to regulate genes — is changing our understanding of cancer and has led to the development of a number of new drugs. These drugs target epigenetic enzymes, which regulate a cell’s genetic programming. Rather than destroy cancer cells, the therapies seek to set the cells on a path back toward normal growth and development. Many cancers are fueled by biochemical changes of histones, the proteins that serve as central cylinder for our DNA. New epigenetic therapies that reverse these changes are showing early promise in clinical trials and likely to be available for treatment in routine medical practice soon.

Research into Metastasis: For over 200 years, scientists have been striving hard to understand metastasis, the process that allows some cancer cells to break off from their tumor of origin and take root in a different tissue. Still today , the problem is as urgent as ever. Metastasis causes nine out of ten deaths from cancer and survival rates from metastatic cancer are essentially remain unchanged in last 50 years. Research focused on metastasis will likely generate new treatments to control cancers that presently are hard to treat. Characterizing circulating tumor DNA cells (liquid biopsies) are likely to help to address the challenge soon.

In nutshell , Genomic Profiling, precision medicine, immunotherapy drugs, cell-based therapies could give medicine a new dimension. New epigenetic drugs could turn cancer cells normal. Understanding and assessing each individuals risk for Cancer will become more precise. A more coordinated and systematic research ,will reduce fragmented efforts of scientists and hopefully will lead to more integrated, personalized care ,which in turn  will make the experience of living with cancer feel less lonely and isolated. It will make the process of preventing and controlling cancer more tailored to the needs of the people.