The history of medicine, stretching as far back as when our human ancestors first roamed the earth, is a poignant volume of how far we have come, and how far we have yet to go.
Take cancer, for example. In the past, when life expectancy was drastically lower, cancer was seen as less of an issue as it is today because people were more likely to die from infectious diseases or war. The Western world has now experienced a time of peace for the last few decades; while this is laudable, it also means that diseases that take time to manifest such as cancer are becoming more common.
The frustrating thing about cancer is that most medical professionals (including medical students) can recite how it spreads once it has formed. It is the greater mysteries that elude us, starting with the greatest of them all: Why? And secondly, how can we outsmart it so that we remain a step ahead instead of playing catch up all the time?
The good news is that cancer research today is infused with purpose and life. A cure is closer than ever before; we can feel it in our bones. Whether or not we will see a cure during our lifetime is a separate question, but we all understand that we must move the needle forward, no matter how minutely.
Metastatic MTC Management
“Complete surgical resection of the thyroid mass and locoregional metastasis is the only curative option for locoregional medullary thyroid carcinoma (MTC),” Kim and Kim wrote in Endocrinology and Metabolism. “Total thyroidectomy is the preferred surgical approach.”
The management plan described by Kim and Kim is the most appropriate route to pursue, at least during early stages of the disease. Nevertheless, surgical resection becomes impossible once the cancer has metastasized.
Studies indicate that about 1 to 2 in every 10 patients will present with distant metastases during diagnosis, while a study assessing the 10-year survivability of patients found that 10% to 40% of MTC metastasized from the time of first diagnosis.
The relatively high figure of metastatic MTC upon presentation is a source of concern, since it means that many patients are either asymptomatic or that the symptoms they experience are so minor that they choose not to see a physician entirely. The public health challenge of our day with regards to oncology will be to ensure that everyone of any cancer type presents early enough for a curative option to remain available, but that is a discussion for another day.
Let’s assume we have a patient in front of us who has just been told that he has metastatic MTC and is not a candidate for curative surgery. This information will no doubt cause him significant distress. Eventually, the inevitable question manifests: “What now, Doctor?”
“Advances in understanding the molecular mechanisms and intracellular signaling pathways involved in MTC pathogenesis have allowed for the development of targeted therapies, offering new perspectives on effective therapies for advanced MTC,” Angelousi and colleagues wrote in Endocrine-Related Cancer.
There are still a number of therapeutic strategies that physicians can pursue to increase quality of life and reduce disease burden. Tyrosine kinase inhibitors (TKIs) work by blocking tyrosine kinase-dependent oncogenic pathways. An increasing number of multitargeted TKIs have been clinically tested to support patients with advanced MTC. Among them are motesanib, sorafenib, sunitinib, axitinib, anlotinib, cabozantinib, and vandetanib.
These drugs should be examined in the context that surgical options have been sealed shut due to the metastasizing of the cancer. Therefore, the chief goals for these forms of therapies are extending overall survival and securing the longest-possible progression-free survival. Scientists should also examine whether these TKIs offer symptomatic relief, and how well.
Aside from currently available drugs, scientists are also looking at various investigational therapies that may yet yield the desired results. Studies indicate that the combination of sunitinib and cisplatin can interfere with the autophagic lysosomal pathway, and that these drugs seem to be active in progressive/metastatic MTC.
The idea of finding the right combination of drugs to prescribe to a patient in order to maximize therapeutic benefits is nothing new. Nonetheless, they consistently produce notable results. A recent study assessing the merits of cytotoxic chemotherapy and TKIs discovered that they synergistically prolonged progression-free survival compared to chemotherapy alone in MTC and other cancers. However, the combination of different drugs may result in new adverse events; these trials should always be conducted in a consistent and controlled environment.
Read more about MTC treatment
Some scientists have advocated for personalized treatment strategies as a means to help patients overcome their diagnosis. Various pathways and alternate targets have been proposed, such as aurora kinase inhibitors, farnesyltransferase inhibitors, and exploiting microRNA levels. New targets, such as minigastrin and glucose-dependent insulinotropic polypeptide receptor (GIPR) have also been highlighted.
At present, the reality is that, aside from surgical resection, other treatments merely extend survival and improve quality of life; they are, in a sense, palliative. Nevertheless, the optimism, passion, and energy of researchers today may mean that a cure for cancer is not too far away.
Kim M, Kim BH. Current guidelines for management of medullary thyroid carcinoma. Endocrinol Metab (Seoul). Published online June 22, 2021. doi:10.3803/EnM.2021.1082
Angelousi A, Hayes AR, Chatzellis E, Kaltsas GA, Grossman AB. Metastatic medullary thyroid carcinoma: a new way forward. Endocr Relat Cancer. Published online May 31, 2022. doi:10.1530/ERC-21-0368