HER3 overexpression in solid tumors is tied to poor prognosis, concretely in breast and non-small-cell lung cancers, where treatment resistance often occurs upon using targeted therapy, highlighting the need for novel targeted therapies against HER3. Since its expression is much higher in tumor than normal cells, HER3 is a robust candidate for antibody-drug conjugate (ADC) therapy.
“I think we’ve come a long way in understanding the importance of this biology. We know it affects men and women, children and adults,” Paul Mischel told the audience during his plenary talk at the 2025 Annual Meeting of the American Association for Cancer Research (AACR 2025). “It’s very prevalent, it’s very devastating. It creates resistance. And we’ve learned some very fundamental rules about this biology that are driving it.”
Neuroblastoma, an aggressive malignancy originating from neural crest cells, accounts for 15% of cancer-related deaths in children. Treatment strategies include systemic chemotherapy, radiation or immunotherapy with anti-GD2 antibodies, all with severe side effects and long-term toxicity. Retinoic acid (RA) has been shown to promote neuroblastoma growth inhibition while suppressing MYCN oncogene expression. However, its effect is reversible, and tumor regrowth may occur.
Researchers from Vicero Inc. have developed a Vincobody platform, which allows for design of novel proprietary VHH antibody fragments that possess the efficacy of dual checkpoint blockade while mitigating the toxicity limitations of current monoclonal antibody therapies.
Combining the direct cytotoxic effects of antibody-drug conjugates (ADCs) with the immune-enhancing properties of immunostimulators represents a new therapeutic strategy that could not only eradicate tumor cells, but also reprogram the tumor microenvironment, leading to durable and systemic anticancer immunity. Using this new approach, researchers from Bioray Pharmaceutical Co. Ltd. developed and characterized of a new dual drug ADC (BiADC), named BR-113, designed to target human (h)Trop2.
RAS G12D is one of the most frequent mutations in RAS, and when it occurs, it leaves RAS in a permanently active state, causing the cell to proliferate uncontrollably. Examples of the so-called RAS-addicted cancers are colorectal cancer or pancreatic ductal adenocarcinoma.
Immunostimulant therapy using agonistic cytokines or activating antibodies has been associated with off-target side effects, failure to preferentially activate cytotoxic lymphocytes (CTLs) over regulatory T cells (Treg), and the development of T-cell exhaustion. With the aim of overcoming these issues, researchers from Recourse Biologics Inc. designed a potentially first-in-class immunostimulatory fusion protein.
Researchers from Cedars-Sinai Medical Center presented the preclinical efficacy of KROS-401, an IL-4/IL-13 blocking peptide that effectively reprograms macrophages in glioma models.
Patients with metastatic or unresectable gastric cancer are usually given 5-fluorouracil (5-FU) and platinum-based chemotherapy, but patients with advance disease usually have a poor prognosis. The use of chemotherapy increased the levels of cyclooxygenase-2 in tumor cells, which in turn increase the levels of prostaglandin E2 (PGE2) in the tumor microenvironment. When PGE2 binds to their receptors EP1 to EP4 on immune cells, it triggers an immunosuppressive tumor microenvironment. The use of the EP2 and EP4 dual antagonist OCT-598 was tested in the preclinical setting for gastric cancer.
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