Throughout modern medical history, we have much to be thankful for regarding the tenacity of medical researchers who would simply not take “no” for an answer, titans who were convinced that science provided the solution to the most pressing maladies of their age. Many scientific discoveries come to mind (and many of these scientists go on to win Nobel prizes in medicine). Take, for example, the discovery of insulin at the start of the 20th century, which ended the reign of diabetes mellitus as an incurable disease.
At Rare Disease Advisor, we are likewise impressed by the tenacity of medical researchers today who, having devised a breakthrough treatment in a particular disease, refuse to see it as the end of the matter. Rather, scientists across the globe, from various backgrounds and nationalities, press forward to find a definite cure for several diseases, undaunted by the challenges ahead, single-minded in their pursuit to change lives for the better via innovations in medicine.
Cholangiocarcinoma is a cancer that can occur at any anatomical location along the biliary tree. In fact, cholangiocarcinoma today is defined according to its anatomical location. Although subtle differences exist between different cholangiocarcinoma subtypes, the overall 5-year survival rates remain poor.
Read more about cholangiocarcinoma etiology
Another challenge of treating cholangiocarcinoma lies in the failure of much of the medical profession to pass through the very first hurdle, namely, the early diagnosis of the disease, at which stage meaningful treatment can still change clinical outcomes. Because cholangiocarcinoma is an insidious disease, developing quietly until the inevitable symptoms spill out into the open, physicians tend to only diagnose this disease when it is at a highly advanced stage.
This means there are 2 obvious strategies for tackling cholangiocarcinoma: improve diagnostic protocol or improve the treatment of the disease at its later stages.
Current Therapeutics for Cholangiocarcinoma
“The majority of new [cholangiocarcinoma] patients (60%-70%) are diagnosed at a late stage and are treated with palliative therapy, particularly chemotherapy,” Wang and colleagues wrote.
Presently, the only effective treatment for cholangiocarcinoma is surgical resection. Unfortunately, this option is only available for patients in the early stages of their disease. Only around 35% of patients with early stages of cholangiocarcinoma qualify for surgical resection. As for chemotherapy, the first-line drugs for advanced cholangiocarcinoma remain gemcitabine and platinum.
Both scientists and patients are beginning to question the orthodoxy on whether palliative care is indeed inevitable for patients who are diagnosed with advanced cholangiocarcinoma. Although palliative care has improved leaps and bounds over the last few years, often providing genuine comfort and symptomatic relief to patients during their dying days, patients and their families are understandably unwilling to accept palliative care as the first form of treatment offered to them.
From a human level, it is difficult to blame patients and their families for thinking that a palliative plan of care suggests that physicians have given up on a cure. Of course, the personal biases of physicians count very little in professional decision-making, since they only act on the best available evidence, and unfortunately, the best available evidence points to palliation as the best recourse for care.
Research into new therapeutics for cholangiocarcinoma has gathered steam in recent years. Researchers are increasingly looking into the molecular profiles of cholangiocarcinoma in order to understand the oncogenic processes taking place in its various subtypes. Currently, cholangiocarcinoma can be broadly categorized into intrahepatic, perihilar, and distal cholangiocarcinoma.
“The prevalence of mutations is highly variable across different studies, potentially in association with regional differences, small sample sizes, or variations in the pathological classification of [intracellular carcinoma] and [extracellular carcinoma] before sequencing,” Wang and colleagues wrote.
Next Generations of Therapeutics
While the public may mistake cancer research as the laser-focused search for a cure for cancer to the exclusion of other aspects of research, in reality, any discoveries made regarding the behavior of a cancer and its contributing factors help scientists in 1 way or another to come closer to finding a cure for this disease.
Scientific researchers are busy mapping out what we know about molecular cholangiocarcinogenesis. The hope, of course, is that the understanding of the molecular processes that contribute to cancer development can aid scientists in nipping in the bud any processes that trigger the carcinogenesis cascade.
“According to the classical belief, cholangiocarcinogenesis is promoted by the dysregulated reparative proliferation of cholangiocytes, which leads to DNA damage, overproduction of mitogenic factors and overactivation of proproliferative intracellular signaling pathways, and subsequently to activating mutations, overexpressed and silenced genes,” Lendvai and colleagues wrote in Pathology & Oncology Research.
Just from this statement alone, we can see that carcinogenesis is a multi-factorial issue; it isn’t as simple as switching an “on-off” button. Instead, careful study on the various cascades that trigger carcinogenesis is needed for scientists to understand the right molecular mechanisms to target to hopefully silence carcinogenesis once and for all.
Scientists are still trying to identify biomarkers that can be used to screen patients who are at a higher risk of developing cholangiocarcinoma in the hopes of commencing treatment early.
“Nevertheless, genome and exome sequencing studies have identified the predominant molecular alterations in [cholangiocarcinoma]and in early lesions of [cholangiocarcinoma],” Lendvai and colleagues wrote.
It is right that we acknowledge the insights that molecular research into cholangiocarcinogenesis has yielded in our collective understanding of the disease. We have every reason to believe that the future of cholangiocarcinoma care will be increasingly personalized, especially when we identify the specific triggers that cause the disease.
Read more about cholangiocarcinoma treatment
“Although the efficacy of molecular targeting agents has been satisfactory so far . . . future developments in genomic screening methods using high-throughput sequencing are expected,” Wang and colleagues concluded. “A comprehensive genome map could also help in the identification of treatment options and provision of personalized treatment for patients with advanced [cholangiocarcinoma].”
Lendvai G, Szekerczés T, Illyés I, et al. Cholangiocarcinoma: classification, histopathology, and molecular carcinogenesis. Pathol Oncol Res. Published online November 17, 2018. doi:10.1007/s12253-018-0491-8
Wang M, Chen Z, Guo P, Wang Y, Chen G. Therapy for advanced cholangiocarcinoma: current knowledge and future potential. J Cell Mol Med. Published online December 4, 2020. doi:10.1111/jcmm.16151