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Fighting rare cancers: lessons from fibrolamellar hepatocellular carcinoma
May 11, 2023

Fighting rare cancers: lessons from fibrolamellar hepatocellular carcinoma

The current issue of Nature Reviews Cancer features on its cover a personal perspective on the fight against rare cancers. One part of the story of this features the use of an agnostic drug-repurposing screen to do functional precions medicine. This revealed vulnerabilities that were not predicted by the transcriptome, but which helped not only elucidate some important cell biology pathways in the toumor, but have laid the foundation for a clinical trial

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A path to translation: How 3D patient tumor avatars enable next generation precision oncology
May 10, 2023

A path to translation: How 3D patient tumor avatars enable next generation precision oncology

3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs require standardization criteria and prospective trials to establish clinical benefits. Innovative trial designs that combine omics and 3D-PTA readouts may lead to more accurate clinical predictors, and an integrated platform that combines diagnostic and therapeutic development will accelerate new treatments for patients with refractory disease.

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Early Functional Precision Medicine Approaches Show Potential to Improve Patient Outcomes
May 9, 2023

Early Functional Precision Medicine Approaches Show Potential to Improve Patient Outcomes

Although functional precision medicine has the potential to transform cancer care, experts at the American Association for Cancer Research's annual meeting recounted how the present regulatory and reimbursement environment has made it difficult for them to use research findings to inform patient treatment.

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Functional Precision Medicine in Oncology
May 8, 2023

Functional Precision Medicine in Oncology

Professor Anthony Letai, President of the Society for Functional Precision Medicine explains the concept of functional precision medicine in oncology: we take the patient's living tissue and expose it to drugs, then ask if there is an effect, we can measure that predicts response in vivo. Dr. Letai is convinced that this will be a valuable diagnostic tool, the next step in precision medicine.

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Complete Remission of Widely Metastatic Human Epidermal Growth Factor Receptor 2–Amplified Pancreatic Adenocarcinoma After Precision Immune and Targeted Therapy With Description of Sequencing and Organoid Correlates
May 3, 2023

Complete Remission of Widely Metastatic Human Epidermal Growth Factor Receptor 2–Amplified Pancreatic Adenocarcinoma After Precision Immune and Targeted Therapy With Description of Sequencing and Organoid Correlates

Drug testing of patient derived tumor organoids identified high sensitivity to the EGFR targeting drug lapatinib, consistent with HER2 amplification.  Remarkably, this patient achieved a complete remission with a combination of EGFR inhibitor trastuzumab and pertuzumab followed by a personalized vaccine, and is currently disease free.  This study indicates the potential of functional testing of patient derived tumor cells to identify effective therapies for cancers with poor outcome.

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Promises and challenges of organoid-guided precision medicine
May 2, 2023

Promises and challenges of organoid-guided precision medicine

Organoids are self-organizing, expanding 3D cultures derived from stem cells. Using tissue derived from patients, these miniaturized models recapitulate various aspects of patient physiology and disease phenotypes, including genetic profiles and drug sensitivities

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Mini-organs attract big pharma
March 27, 2023

Mini-organs attract big pharma

The accompanying news story discusses how big Pharma, in this case Roche, saw the light and realizedthat patient derived tumor model, which share both somatic and germlinegenetics of a given patient would be a useful model system for both drug development and precision medicine. It is only a matte of time until others catch on.

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Patient-derived organoids as a predictive biomarker for treatment response in cancer patients
March 27, 2023

Patient-derived organoids as a predictive biomarker for treatment response in cancer patients

A roadblock to acceptance of ex vivo drug testing using patient derived tumor cells is demonstration of clinical utility, specifically prospective evidence of patient response. The attached review by Wensink et al. summarizes findings from 17 different studies and concludes that ‘The currently available results offer an optimistic perspective that individualized tumour response testing using PDO shave clinical validity as a predictive biomarker for cancer patients. The pooled sensitivity and specificity for discriminating patients with a clinical response through PDO-based screening were 0.81 (95% CI 0.69–0.89) and 0.74 (95%CI 0.64–0.82), respectively.'

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Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy
February 21, 2023

Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy

Precision medicine is starting to incorporate functional assays to evaluate anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and extensively been used to predict treatment efficacy in different types of cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events (‘priming’) and anticipate therapy-induced cell death leading to tumor elimination. This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, that limits drug screening on patient samples, especially in solid tumors.

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BCL-2 Inhibitors: Driving Cells to Destruction
February 20, 2023

BCL-2 Inhibitors: Driving Cells to Destruction

The story begins decades ago with a man named Stanley Korsmeyer, who led the molecular oncology program at Dana-Farber from 1998 until his death in 2005. He discovered that B-cell cancers like CLL over-produced a protein called BCL-2, and interfered with apoptosis, or programmed cell death. But how that went from an interesting discovery to a game-changing cancer drug is a story of persistence and momentum, and it’s the first episode of season two of Unraveled

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