How to Cure Metastasis

BY Dr. Rajeev Samant


It is very clear that the primary cause of morbidity and mortality in cancer patients is metastases. Though cancers such as breast cancer are a consequence of uncontrolled cell division, their spread and growth at the distant sites in the patient body presents a formidable challenge. Excellent advances in surgery, imaging and radiation technologies have rendered removal of the primary tumor a process that is less invasive and much more effective than ever before. Continued efforts in improving these technologies with added efforts in early detection and prevention are certainly essential and beneficial. However, curing metastasis will be a critical battle that we will have to win to ensure the eventual win in the war on cancer. Let us take the example of breast cancer for discussion. There are key points.  Firstly, metastatic dissemination can occur very early in tumor progression and then the metastasized cell can stay in a clinically undetectable, dormant form, for prolonged time.

Over last 25 years researchers have made notable contributions to the field of metastasis. Dr. Fidler, defined and highlighted metastasis as the threat to cancer patients. Dr. Folkman and Dr. Jain showed that recruitment of blood vessels to the tumor offers an escape route for the metastatic cells and that this process could be clinically targeted. Dr. Bissell led the efforts in defining the role of extracellular matrix in shaping the characteristics of cancer. Dr. Matrisian and others showed the importance proteases in dissociating the physical barriers posed by the matrix surrounding the escaping cells. The landmark discoveries of metastasis promoting and metastasis suppressing genes through efforts led by Drs. Steeg, Chambers, Welch, Kumar and others enabled researchers to start deciphering the molecular underpinning of the complex process of metastasis. Simply put however, a successful metastatic cancer cell is a wrong cell at a wrong place at the right time (or waiting for the right time).

The Metastasis Research Society is an active international society of several hundred dedicated scientists with a mission to understand and cure metastasis. The recent biennial meeting of this society brought to light that the following are the key challenges or frontiers towards our efforts in curing metastasis. One of them is to define how the cells gain capability to escape? A process called as epithelial-mesenchymal-transition seems to be one of the potential answers. The second one is why the cells get to a specific secondary site? For example, why does breast cancer metastasize to bone or brain but not to some other organs. The third one is can we detect metastatic cells early? Towards the later, Drs. Pantel and Haber have pioneered marvelous technologies for detection of circulating tumor cells (CTCs). The idea is that the non-invasive sampling of blood will be readout of the activities of the primary tumor towards metastatic dissemination. Modification and advances in these strategies will allow more personalized management of metastasis.  However, that wrong cell at wrong destination can wait for the right time and thus survivors of metastatic cancers such as breast, prostate cancers or melanoma are always living in a shadow of fear. The key to this dormancy of cells is getting defined by efforts from laboratories of Drs. Ann Chambers and Aguirre-Ghiso. Additionally, of course we can’t ignore the inability of the immune cells to get alerted about these wandering metastatic cells. In our future articles we will definitely highlight the efforts on that front.  Collectively, these very important and genius efforts are promising take us to a higher ground and advance to a victory in this battle.

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