BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Vrije Universiteit Amsterdam//NONSGML v1.0//EN NAME:PhD defence S. Mobach METHOD:PUBLISH BEGIN:VEVENT DTSTART:20260619T114500 DTEND:20260619T131500 DTSTAMP:20260619T114500 UID:phd-defence-s-mobach@8F96275E-9F55-4B3F-A143-836282E12573 CREATED:20260925T014050 LOCATION:Main building VU, 1105, Aula, De Boelelaan, 1081 HV, Amsterdam SUMMARY:PhD defence S. Mobach X-ALT-DESC;FMTTYPE=text/html:

Detection and pharma cological disruption of CXCR4 oligomerization in lymphoid neoplasms

Research opens door to more effective treatment of lymphom a cancer

Lymphoid cancers arise from lymphocytes, a type of white bloo d cell that is part of the immune system. Although treatment for thes e cancers has improved greatly in recent years, a proportion of patie nts still experience recurrence of the disease. A major cause is that cancer cells can hide in protective places in the body, such as the bone marrow and lymph nodes. There, they receive signals that stimula te their growth and survival and make them less sensitive to therapy.

Central to the study was the protein CXCR4. This protein is lo cated on the surface of cancer cells and helps cells move through the body. Mobach discovered that CXCR4 not only acts as a separate prote in, but often comes together in small groups called clusters. Using n ewly developed nanobody technology, these clusters could be accuratel y visualized for the first time in both cancer cells and patient mate rial.

The study shows that these CXCR4 clusters play an importa nt role in properties that make cancer cells stronger, such as their ability to move and resist therapies. When Mobach took apart the clus ters containing small molecules, nanobodies and antibodies, the behav ior of the cancer cells changed. They moved less well and became more sensitive to existing drugs.

Notable was the effect on venetoc lax, a drug already used in certain blood cancers. In the study, this drug worked better after the CXCR4 clusters were disrupted. Mobach: This suggests that combination therapies may be more successful in th e future."

For patients with lymphoid cancer, this approach cou ld contribute to treatments that are more successful and remain effec tive longer. In addition, the research has developed new antibody-lik e molecules that can target CXCR4. These could be further tested in f uture preclinical studies and clinical trials.

The findings are in line with a broader development within oncology: making treatment s increasingly targeted and personalized. By better understanding how cancer cells protect themselves from therapy, researchers hope to de velop new strategies to break through that protection.

Learn mo re about the dissertation

DESCRIPTION: Detection and pharmacological disruption of CXCR4 oligome rization in lymphoid neoplasms

Research opens door to more effect ive treatment of lymphoma cancer

Simon Mobach discovered a possib le new way to make lymphoid cancers more sensitive to existing therap ies. The study shows that disrupting so-called CXCR4 clusters on canc er cells causes these cells to be less protected from drugs. This cou ld lead to more effective treatments in the future for patients in wh om the disease recurs.Lymphoid cancers arise from lymphocytes, a type of white blood cell that is part of the immune system. Although trea tment for these cancers has improved greatly in recent years, a propo rtion of patients still experience recurrence of the disease. A major cause is that cancer cells can hide in protective places in the body , such as the bone marrow and lymph nodes. There, they receive signal s that stimulate their growth and survival and make them less sensiti ve to therapy.Central to the study was the protein CXCR4. This protei n is located on the surface of cancer cells and helps cells move thro ugh the body. Mobach discovered that CXCR4 not only acts as a separat e protein, but often comes together in small groups called clusters. Using newly developed nanobody technology, these clusters could be ac curately visualized for the first time in both cancer cells and patie nt material.The study shows that these CXCR4 clusters play an importa nt role in properties that make cancer cells stronger, such as their ability to move and resist therapies. When Mobach took apart the clus ters containing small molecules, nanobodies and antibodies, the behav ior of the cancer cells changed. They moved less well and became more sensitive to existing drugs.Notable was the effect on venetoclax, a drug already used in certain blood cancers. In the study, this drug w orked better after the CXCR4 clusters were disrupted. Mobach: This su ggests that combination therapies may be more successful in the futur e."For patients with lymphoid cancer, this approach could contribute to treatments that are more successful and remain effective longer. I n addition, the research has developed new antibody-like molecules th at can target CXCR4. These could be further tested in future preclini cal studies and clinical trials.The findings are in line with a broad er development within oncology: making treatments increasingly target ed and personalized. By better understanding how cancer cells protect themselves from therapy, researchers hope to develop new strategies to break through that protection.Learn more about the dissertatio n END:VEVENT END:VCALENDAR