Exploring the Crucial Role of Biosamples in Advancing Clinical Trials for Cancer and Parkinson’s

In the eerie glow of the hospital's LED lights, nurse Claire noticed something unsettling in the eyes of patient 000001, who'd received CogniVance a week prior. There was a shimmer, unnatural and piercing, that seemed to dance in her gaze—an usher of the unknown effects of the drug designed to push the limits of human cognition. With urgency, Claire opened a lab kit and drew blood to test for the elusive biomarker of mental stability. She heard the clock strike midnight in the nearby church. There was no time to wait for the morning to ship this blood for testing - the poor FedEx guy always got lost in the hospital's labyrinth anyway.

Outside, the world lay in a deep slumber, unaware of the drama unfolding within the hospital walls. For Roan, though, the night was alive, throbbing with the thrill of the ride and the mission. The package he was to deliver held the key to understanding the strange phenomena observed in the patient. The city's labyrinthine streets became a blur as he raced against time, a lone figure against the backdrop of a sleeping world, carrying a cargo that could redefine the boundaries of human potential.

Let's allow Roan to race into a freaky unknown - until the next time - and land firmly into the exciting madness land we call clinical trials. In this land, one of the key characters is Biosample. He is a shy fella, the kind who is typically hanging out in the background, clinging to the walls of the dancing floor until his time. And then… Wham! Bam! He kung fu the cocky Data straight into the guts leaving him cold and unconscious by the FDA parlor. In our story, though, Biosample is the protagonist. He will take us on a heart-pounding journey from a shy village boy to a rightful member of the Hall of Heroes. This story is a documentary of his deeds.

Chapter 1

Setting: Biobank

??A newly published paper on physical activity and sleep patterns in Parkinson's disease (PD) leverages data from the UK Biobank to explore the impact of physical activity and sleep patterns on the risk of PD, revealing significant findings that could alter preventive strategies in the field. By analyzing over 339,000 participants, the research uncovered that individuals with high levels of physical activity (≥ 3000 MET-minutes/week) and those with optimal sleep patterns (a score of ≥ 3 in areas such as chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) were at a lower risk of developing PD. Notably, the combination of both high physical activity and ideal sleep patterns conferred the most significant reduction in PD risk, suggesting that lifestyle modifications could serve as a key component in PD prevention. For reference, 3000 MET equates to 556 min of walking at 3.7 mph. What I find interesting is that the CDC's recommendation of ~1000 MET-minutes/week falls short of this and other recent findings if the target of the physical activity is to achieve maximum health benefits. As a side comment, if you want to learn how to integrate physical activity into your daily life, Andrew Huberman provides a comprehensive toolkit on this Huberman Lab Podcast site. But, back to the article.

The utilization of the UK Biobank database underscores the critical role of biobanks in enabling comprehensive epidemiological studies. There are a few things, however, we can do to further support biobanks in their contribution to future research. We can make additional efforts to? focus on expanding the diversity and depth of data collected, encompassing a broader range of environmental, genetic, and lifestyle factors. Additionally, improving data accessibility and interoperability between biobanks can facilitate multidisciplinary research, enabling a more nuanced understanding of disease mechanisms.

Characters: Protagonist's Sidekick - Preanalytical Variables

??A paper recently published in the Journal of Translational Medicine presents a comprehensive comparison of mismatch repair deficiency (dMMR) detection via immunohistochemistry (IHC) and microsatellite instability (MSI) using PCR in a large cohort of cancer patients (n=1306), highlighting significant discrepancies (19.3%) between these two diagnostic methods across various cancer types. Notably, the study underscores the low sensitivity of MSI PCR relative to MMR IHC, with a kappa correlation coefficient below the acceptable threshold of 0.7, suggesting a lack of concordance that challenges current clinical practices which treat these tests as equivalent for guiding immunotherapy decisions.

To decipher a "sci-speak":

Mismatch repair deficiency - the absence of DNA "autocorrect" function in our cells. Microsatellite instability - a repeat of the same typos over and over due to fault of "autocorrect".

Kappa correlation?coefficient - imagine you and your friend sit in the same? park and count birds; at the end of the day, you compare your numbers; if the number is 1, you counted precisely the same number of the same types of birds. If the number is 0 - your counts would be no better than random guessing; if the number is -1 - it means that your and your friend's counts are exactly opposite, which indicates a systemic error (e.g., you don’t have an agreement on how each bird looks).

This research identifies the potential role of preanalytical variables, such as tissue fixation quality and tumor cellularity, as significant contributors to the observed discrepancies rather than technical errors or tumor type. This insight stresses the need for stringent standardization and control of preanalytical factors to ensure reliable diagnostic outcomes. This study is a crucial step towards enhancing the precision of cancer diagnostics and tailoring immunotherapeutic approaches, highlighting the need for an interdisciplinary focus on the preanalytical phase of cancer biomarker testing.

??A new study in the Journal of Liquid Biopsy explores the use of liquid biopsy, specifically circulating tumor DNA (ctDNA), for monitoring minimal residual disease (MRD) in patients with non-small cell lung cancer (NSCLC) post-radical treatment. The research underscores the potential of ctDNA as a non-invasive marker for early detection of disease recurrence, providing a promising alternative to traditional biopsy methods. However, a significant finding of the study is the substantial impact preanalytical variables—such as the methods used for blood collection, processing, and storage—have on the variability of ctDNA extraction, which can influence cell-free DNA (cfDNA) analysis outcomes. The study reports up to 50% variability (!) in cfDNA yield due to differences in preanalytical procedures, highlighting the critical need for standardized protocols to ensure reliable and reproducible results. The findings advocate for further research into standardizing preanalytical processes to enhance the accuracy and applicability of liquid biopsy in cancer management, positioning it as a valuable tool in the personalized treatment and monitoring of NSCLC patients.

As it is tough to come up with a dramatic cliffhanger when it comes to curated content, I'll leave you with a call to action instead. If you liked what you have just witnessed, if you have an undying passion for biosamples, or if you just like plain weirdness:

??Share, Like, and definitely, Comment!

We will return to the Biosample fella (and, of course, Roan) in two weeks +/- 1 day.

?P.S.:? If you have found the image of collection tubes dancing on the container strapped precipitously to the bike's rack unsettling, please reach out to get your IATA certification. If you don’t know what IATA is, you definitely need to come back for more stories!