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:2026/phd-defence-s-mobach@8F96275E-9F55-4B3F-A143-836282E12573 CREATED:20260612T030920 LOCATION:Hoofdgebouw, Aula De Boelelaan 1105 1081 HV Amsterdam SUMMARY:PhD defence S. Mobach X-ALT-DESC;FMTTYPE=text/html:

Detection and pharmacol ogical disruption of CXCR4 oligomerization in lymphoid neoplasms

Research opens door to more effective treatment of lymphoma cance r

Lymphoid cancers arise from lymphocytes, a type of white blood cell that is part of the immune system. Although treatment for these cance rs has improved greatly in recent years, a proportion of patients sti ll experience recurrence of the disease. A major cause is that cancer cells can hide in protective places in the body, such as the bone ma rrow and lymph nodes. There, they receive signals that stimulate thei r growth and survival and make them less sensitive to therapy.

Central to the study was the protein CXCR4. This protein is located o n the surface of cancer cells and helps cells move through the body. Mobach discovered that CXCR4 not only acts as a separate protein, but often comes together in small groups called clusters. Using newly de veloped nanobody technology, these clusters could be accurately visua lized for the first time in both cancer cells and patient material.

The study shows that these CXCR4 clusters play an important role in properties that make cancer cells stronger, such as their ability to move and resist therapies. When Mobach took apart the clusters co ntaining small molecules, nanobodies and antibodies, the behavior of the cancer cells changed. They moved less well and became more sensit ive 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 cont ribute to treatments that are more successful and remain effective lo nger. In addition, the research has developed new antibody-like molec ules that can target CXCR4. These could be further tested in future p reclinical studies and clinical trials.

The findings are in lin e with a broader development within oncology: making treatments incre asingly targeted and personalized. By better understanding how cancer cells protect themselves from therapy, researchers hope to develop n ew strategies to break through that protection.

Learn more abou t the dissertation

DESCRIPTION:

Research opens door to more effective treatment of ly mphoma cancer

Simon Mobach discovered a possible new way to make lymphoid cancers more sensitive to existing therapies. The study sho ws that disrupting so-called CXCR4 clusters on cancer cells causes th ese cells to be less protected from drugs. This could lead to more ef fective treatments in the future for patients in whom the disease rec urs. Lymphoid cancers arise from lymphocytes, a type of white blood c ell that is part of the immune system. Although treatment for these c ancers has improved greatly in recent years, a proportion of patients still experience recurrence of the disease. A major cause is that ca ncer cells can hide in protective places in the body, such as the bon e marrow and lymph nodes. There, they receive signals that stimulate their growth and survival and make them less sensitive to therapy. Ce ntral to the study was the protein CXCR4. This protein is located on the surface of cancer cells and helps cells move through the body. Mo bach discovered that CXCR4 not only acts as a separate protein, but o ften comes together in small groups called clusters. Using newly deve loped nanobody technology, these clusters could be accurately visuali zed for the first time in both cancer cells and patient material. The study shows that these CXCR4 clusters play an important role in prop erties that make cancer cells stronger, such as their ability to move and resist therapies. When Mobach took apart the clusters containing small molecules, nanobodies and antibodies, the behavior of the canc er cells changed. They moved less well and became more sensitive to e xisting drugs. Notable was the effect on venetoclax, a drug already u sed in certain blood cancers. In the study, this drug worked better a fter the CXCR4 clusters were disrupted. Mobach: This suggests that co mbination therapies may be more successful in the future." For patien ts with lymphoid cancer, this approach could contribute to treatments that are more successful and remain effective longer. In addition, t he research has developed new antibody-like molecules that can target CXCR4. These could be further tested in future preclinical studies a nd clinical trials. The findings are in line with a broader developme nt within oncology: making treatments increasingly targeted and perso nalized. By better understanding how cancer cells protect themselves from therapy, researchers hope to develop new strategies to break thr ough that protection. Learn more about the dissertation Detec tion and pharmacological disruption of CXCR4 oligomerization in lymph oid neoplasms END:VEVENT END:VCALENDAR