erlotinib

The X-ray crystallographic analysis revealed the binding mode of 43 within the PHGDH active site. These findings provide a foundation for developing PHGDH-targeted anticancer therapies.

In vivo studies have shown that knockdown of SOX4 or administration of erlotinib significantly inhibited tumor growth and reduced the rate of lymph node metastasis. SOX4 promotes the growth and lymph node metastasis of LSCC by regulating PTBP2. The SOX4-PTBP2 axis may become a potential diagnostic and therapeutic target for LSCC.

P1, N=85, Terminated, Boundless Bio, Inc. | Trial completion date: Mar 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Mar 2026; Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.

SUCLG2 overexpression conferred erlotinib resistance in vitro, whereas its depletion restored TKI sensitivity and impaired xenograft tumor growth, effects that were rescued by VEGFA reconstitution...In clinical specimens from CRPC patients and NEPC patient-derived xenografts, progressive nuclear co-accumulation of SUCLG2 and EGFR alongside elevated VEGFA expression correlated with disease advancement. Collectively, these findings define a non-canonical nuclear SUCLG2/EGFR/VEGFA signaling axis that mediates NEPC progression and therapeutic resistance, providing mechanistic rationale for combined SUCLG2 and EGFR inhibition as a strategy to overcome treatment resistance in this lethal malignancy.

This case demonstrates the effectiveness of first-generation TKIs in treating metastatic EGFR-positive NSCLC, particularly in countries that cannot afford recent targeted therapies. In addition, it describes a rare adverse effect that was well tolerated and managed successfully.

Erlotinib 150 mg/day was introduced based on reports of dose‑dependent CNS efficacy, resulting in prompt improvement of neurological symptoms; however, grade 3 thrombocytopenia led to treatment interruption, followed by rapid neurological decline and death. This case illustrates that reduced‑dose EGFR TKI therapy, even with a CNS‑penetrant agent such as osimertinib, may provide insufficient cerebrospinal fluid drug exposure to prevent CNS progression. Clinicians should recognize that dose modification necessitated by adverse events may compromise CNS control, and vigilant monitoring for neurological symptoms is essential in patients receiving reduced‑dose EGFR TKIs.

These findings challenge the prevailing notion that lysosomotropic delivery sequesters kinase inhibitors away from their cytoplasmic targets. Our study highlights the potential of rational probe design to manipulate subcellular localization while preserving functional engagement with oncogenic kinases, opening new avenues for targeted bioimaging and therapeutic delivery.

Leads 12c, 12i, and 22 demonstrated potent kinase inhibition, with 22 yielding a CDK-2 IC₅₀ of 0.03 µM (seliciclib: 0.02 µM), and 12c delivering an EGFR IC₅₀ of 0.12 µM (erlotinib: 0.01 µM). Promising ADMET profiles and good drug likeness are evident in these leads. These data underscore the great potential of this scaffold for developing dual EGF/CDK-2 inhibitors aimed at resistance mechanisms in more aggressive cancers and can thus be pursued further in preclinical optimization.

P1, N=140, Completed, AstraZeneca | Active, not recruiting --> Completed

P1/2, N=4, Terminated, The University of Texas Health Science Center at San Antonio | N=44 --> 4 | Trial completion date: Sep 2027 --> May 2026 | Recruiting --> Terminated | Trial primary completion date: Sep 2027 --> May 2026; Investigational drug limitations

Compounds JRC-2 and JRC-6 exhibited potent antiproliferative effects against MCF-7 breast cancer cells, with IC50 values of 4.59 ± 0.23 µM and 4.01 ± 0.14 µM, respectively, outperforming erlotinib (IC50 = 9.39 ± 0.16 µM). Notably, JRC-6 displayed microtubule-stabilising activity comparable to that of paclitaxel and induced ROS generation, mitochondrial membrane depolarisation, and G2/M phase cell cycle arrest. Molecular docking and molecular dynamics simulations confirmed stable binding of compounds at the EGFR ATP-binding site and the tubulin taxol-binding site.

Immunohistochemistry of the ascitic fluid revealed an EGFR L858R mutation. This case highlights the possibility of false-negative results on initial testing and suggests the potential benefit of EGFR-TKIs, even in EGFR mutation-negative cases at diagnosis.