Understanding Cancer Metastasis: Insights from the Coursera and JHU Course

Introduction

Cancer, characterized by uncontrolled cell growth, remains a formidable challenge in the field of medicine. Cancer becomes even more challenging when it spreads from the primary site to other distant sites of the body . This is known as metastatis and it plays a pivotal role in the progression and ultimate outcome of the disease. Having completed the “Understanding Cancer Metastasis” course on Coursera, offered by Johns Hopkins University (JHU), I gained invaluable insights into the intricate processes that define cancer metastasis, its impact on patients’ suffering (morbidity) and death (mortality).

Metastasis: A Historical Perspective

Coined in 1829, the term ‘metastasis’ comes from Greek. It means a migration or a removal. Steven Paget’s seminal 1889 paper, “The Distribution of Secondary Growths In Cancer Of The Breast,” introduced the “seed and soil hypothesis,” postulating that cancer cells (seed) thrive in specific environments (soil). This groundbreaking idea laid the foundation for understanding the organ-specific nature of metastasis.

Key Steps in Metastasis

Metastasis involves a series of steps, including primary tumor growth, angiogenesis, epithelial-mesenchymal transition (EMT), intravasation into the bloodstream, survival during circulation, extravasation at secondary sites, and subsequent growth. The remarkable biological feat lies in the ability of cancer cells to navigate through these intricate steps, with only a fraction successfully completing the journey to metastasize.

Clincal impact

Clinical Dormancy: A Hidden Challenge

Despite surgical interventions to remove the primary tumor, cancer patients often experience relapse after years or even decades. Surgey does cure a percentage of the patients but not all. For example, 62% of breast cancer deaths occur 5 years after surgery. This phenomenon is attributed to clinical dormancy, a period where residual cancer remains undetectable. In early 1950s, pathologist Rupert Willis observed that the time to clinical relapse for several cancers could be between 5 and 30 years. The only plausible explanation, he suggested, was that the cancer cells go in a dormat state. Essentially they remain inactive and reemerge later. This makes cancer even more scary. Much of this is an area of ongoing research.

Metastatic Cancer: Beyond Organ Failure

It may be surprising to learn that metastatic cancer seldom leads to death through organ failure. Liver and lung metastases, for instance, can progress significantly before causing organ-specific morbidity. The staggering realization is that even with 90% liver involvement, normal liver function can persist.If damages to liver goes beyond 90%, the patient can have jaundice, nausea, and ultimately die from liver failure but that would mean literally 90% of liver has to be destroyed. Similarly, for lung there needs to be a lot of metastases before the patient has respiratory failure.

The question arises: if not organ failure, what causes death in metastatic cancer patients? The answer lies in cancer poison syndromes, where chemokines and cytokines, typically essential for normal bodily functions, become agents of harm when overproduced by cancer cells.

Cancer Poison Syndromes: Unmasking the Culprits

Cancer poison syndromes manifest in three main ways:

1. Cachexia: Affecting up to 50% of all cancer patients and 80% of terminal cases, cachexia leads to irreversible loss of body mass, appetite, and weakness. Cytokine overproduction targets various body sites, disrupting hunger centers in the brain and altering protein consumption, fat, and liver metabolism. Cachexia emerges as an immediate cause of death for 20 to 40% of cancer patients.

2. Thrombosis: Approximately 20% of patients suffer from blood clots which can cause swelling and pain where they occur. If they occur in major organ like lung, it can lead to the death of the patient from pulmonary embolism.

3. Pain: Metastatic cancer in bones unleashes cytokines and MMPs, damaging bones and causing tremendous pain. Increased requirement of narcotics for pain relief, often leading to sedation, coupled with the interplay of cachexia could eventually lead to the demise of the patient.

Conclusion

The journey through “Understanding Cancer Metastasis” has illuminated the multifaceted nature of this formidable disease. Beyond the textbook definitions, the course provided a deeper understanding of the challenges posed by metastasis, shedding light on the intricacies of clinical dormancy, the enigma of cancer-related mortality, and the role of cancer poison syndromes in shaping the fate of patients. These insights certainly help us undestand metastasis and its clinical impact better, and gives us a glimpse of the challenges that the patients, clinicians and researchers are dealing with.