October 23, 2023 – Cancer neuroscience is emerging as an innovative field of research in oncology with a potential to identify novel therapeutic targets in the tumour microenvironment (TME). This is particularly relevant for colorectal cancer (CRC) given the unique role of the brain–gut axis (BGA) in GI physiology and pathology. The increasing attention on the essential role of the TME in cancer has shed light on the complex contribution provided by neural mediators to CRC growth and progression. Notably, targeting tumor neurotransmitter signaling and neurotrophic factors in the TME holds promise to be effective alone or in combination with targeted therapies. In fact, a close connection between neural signaling molecules and known druggable cancer-related pathways has been established, particularly angiogenesis, RAS/MAPK signaling and immunomodulation. Therefore, pharmacological manipulation of neurotransmitter pathways may improve the efficacy of existing targeted treatments.

January 18 2023 -Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden; a retrospective cohort study. Genomic signatures contributing to high tumour mutational burden (TMB-H) independent from mismatch-repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status are not well studied. This research aims to characterize molecular features of microsatellite stable (MSS) TMB-H gastrointestinal tumours. Study confirmed that not all mutations related to TMB-H can enhance antri-tumour immune response. More composite biomarkers should be investigated (eg. mTMB signature) to tailor treatment with immune checkpoint inhibitors. Our data also provides novel insights for the combination of immune checkpoint inhibitors and drugs targeting cyclin D1. 

March 2023 -This study explored the association and impact of genetic variants SNPs in the lipid metabolism pathway on progression-free survival and clinical outcomes in metastatic colorectal cancer patients receiving bevacizumab-based first-line treatment, using genetic and clinical data from FOLFIRI-bevacizumab cohorts in randomised trials, a retrospective analysis of FIRE-3 and MAVERICC trials. Our study demonstrates for the first time, to our knowledge, that FASN polymorphisms may predict outcome of bevacizumab-based treatment in patients with mCRC. These findings support a possible role of the lipid metabolism pathway in contributing to resistance to anti-VEGF treatment.

In January 31, 2022 -WunderGlo Director Dr. Heinz-Josef Lenz was named one of the Top Doctors of Oncology in 2022 by The L.A. Business Journal. April 1, 2022 Dr. Heinz-Josef Lenz appointed as the inaugural Deputy Director for Research Programs at USC Norris Comprehensive Cancer Center. On November  21, 2022: WunderGlo Director Heinz-Josef named one of the top distinguished researchers in the world, recognized for his laboratory’s high quality research and the impact he is making across the scientific community (and he is the only physician on this list). 

Build up your muscles in the fight against cancer! – Dr Lenz’s team of colorectal cancer researchers have identified a metabolic pathway which is responsible for muscle build up but also for immune cell response in tumors. Modifying genes involved in this nucleotide pathway significantly changes the sensitivity of immune therapies and activates critical immune cells in the tumor microenvironment. Early collaborations show that immune cells communicate through a sophisticated system with cancer cells, allowing them to migrate, spread, and settle at unique spots in the body such as the liver – dependent on the communication pathways. Data from this unique and extensive collaboration between Dr. Lenz and experts in neuroscience and the tumor micro-environment – brings hope of leading to novel prevention and treatment strategies for colorectal cancer.

Dr Lenz’s team and colorectal cancer researchers throughout the world have identified that Circadian Rhythm predicts outcomes in colon cancer. They have characterized all critical genes in the regulation of the clock in tumor cells and have made significant progress in “Clocking the Tumor” –  meaning that they can treat with novel agents to put the clock  – back into the tumor cells. They have seen in cell-lines and mouse models – that they can kill colon cancer cells very effectively in tumors that are sensitive to immunotherapies. Their compounds are AS effective – and may be even more effective than the approved immunotherapies. -And these treatments can be taken orally by mouth – with very little side effects. 

Parkinson’s Nerve Colon Cancer Project: Dr. Lenz was one of the first to find that patients with Parkinson’s Disease seem to be protected against colon cancer. His group extensively studied the impact of Parkinson Signaling with the outcome in colorectal cancer patients and they found that Parkinson genes are significantly associated with the efficacy of chemotherapy & targeted antibodies in patients with metastatic disease. Very little is known about the connection of the nervous system and cancer cells. But when collaborations began with neuroscientists at USC, it became clear that other neuro-degenerative diseases are also related to colon cancer outcomes. Early collaborations show that nerve cells communicate through a sophisticated system with cancer cells, allowing them to migrate, spread, and settle at very unique spots in the body such as the liver – dependent on the communication pathways between nerve cells and colon cancer cells. Data from this unique and extensive collaboration in neuroscience and the tumor micro-environment – will potentially lead to novel prevention and treatment strategies for colorectal cancer.

March 2020 – Dr. Heinz-Josef Lenz Baricitinib Clinical Trial receives FDA Approval- the first Covid Trial at USC Norris – Dr. Lenz’s tireless work and dedicated lab research – brought amazing insights through a repurposed drug treatment discovery for Covid-19 – that received FDA approval – with the purpose of protecting major organs from damage by the virus, especially to the lungs & kidneys.

The Circadian Clock Protein Research Project suggests that genetic variations in the dopamine signaling pathway might indicate how a patient with advanced colorectal cancer would respond to treatment. The dopamine signaling pathway is part of what researchers call the Brain-Gut Axis, which is a line of communication between the brain and gut to regulate digestive function. Regarding colon cancer, “clock proteins” are shown to be associated with a bad prognosis. For example, night shift workers/flight attendants have higher risk of colon cancer, as this regulation of night/day is based on clock proteins. Our research is showing that Interference with clock proteins in cancer is showing promising anti-tumor effects.

Powerpoint Presentation Update on Molecular Targeted Therapies for Metastatic Colorectal Cancer by Dr. Heinz-Josef Lenz presented at GI ASCO San Francisco – January 2020.

On Tuesday, April 21st, 2020 WunderGlo Foundation Director, Dr. Heinz-Josef Lenz, MD, presented abstract research data: Molecular Landscape of Metastatic Colorectal Cancer – during Grand Rounds at USC Norris Comprehensive Cancer Center. Recent biomarker research in colorectal cancer has been remarkably progressed and assisted early drug development, especially molecular targeting agents in colon cancer. To evaluate the true value of a candidate or approved biomarker, the timing of testing and change of characterization by tumor environment such as previous treatment should be always considered when choosing patients and deciding treatment strategy. Liquid biopsy will become a standard method to non-invasively monitor dynamic changes in tumor genome during treatment that provides us better understanding about decision-making in the treatment of cancer patients. New classification such as CMS will be integrated in prospective clinical trials and hopefully speed up identification of novel therapies depending on activated pathways. Recent data showing promising results using NGS in patients with mCRC.

August 2020: In the News: WunderGlo Director, Dr. Heinz-Josef Lenz explains the exciting insight on the therapeutic approaches that are shaking up Third-Line Treatments for colorectal cancer patients. A wave of novel third-line therapeutic options have shown promising efficacy in patients with colorectal cancer (CRC), according to Heinz-Josef Lenz, MD, FACP, and refined technologies capable of detecting circulating tumor DNA (ctDNA) have opened the door to novel targets and a stronger understanding of disease biology, allowing for more informed treatment decisions. “In the third-line treatment setting for metastatic CRC, we are relying on the molecular subtyping of this disease because we understand that colon cancer is not just 1 disease. We already use the RAS mutation and we now use specific treatments for BRAFmutations,” said Lenz. “Another very interesting and important subgroup is those with HER2 overexpression and/or amplification. Several clinical trials [are examining] compounds [that are] showing very promising and exciting efficacy in this patient population.”

Most Colorectal cancers have spread before diagnosis when the initial tumor is detected, according to a new Stanford study of nearly 3,000 patients by researchers at the Stanford University, led by The Wunder Project Member, Dr. Christina Curtis.  Study emphasizes that Identifying patients in whom early metastasis is likely could better guide treatment decisions.The research was supported by the National Institutes of Health (grant DP1-CA238296), the American Cancer Society, the Wunderglo Foundation, the Emerson Collective Cancer Research Fund, the Innovative Genomics Initiative and the National Cancer Institute.