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Prognostic information for patients with ovarian cancer is captured in clinico-genomic data, histopathology slides and computed tomography imaging; however, how to integrate these data is unclear. A study now presents a method for combining complementary data types to stratify risk and aid treatment selection in patients with ovarian cancer.
Therapy resistance limits the clinical success of tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer. A study now proposes a framework to identify compound resistance mutations to the lorlatinib TKI and provides structure-based drug design approaches to overcome resistance mediated by ALK(G1202R) or ALK(I1171N/S/T).
The lethality of prostate cancer is driven by its progression to a castration-resistant state. A new study identifies gremlin 1 (GREM1) as an agonist of fibroblast growth factor receptor 1 (FGFR1) that drives such progression when androgen receptor (AR) signaling is low, nominating GREM1 as a therapeutic target for prostate cancer with low AR activity.
Acute myeloid leukemia (AML) is characterized by distinct genetic and molecular alterations, including rearrangements in the mixed lineage leukemia (MLL) gene. A study now presents a therapeutic strategy for MLL-rearranged (MLL-r) AML that exploits a unique co-dependency on IKAROS and MENIN.
Patients with cancer are known to be at increased risk of infection and severe complications from COVID-19, with vaccination being key for their protection. A prospective study now evaluates the effect of vaccination against COVID-19 on the immune response mounted by patients with lymphoma.
Cancer vaccines can elicit tumor-specific T cells, but sustaining their function via immune checkpoint therapy (ICT) may be required for robust anti-tumor immunity. A new study reveals that neoantigen cancer vaccines synergize with anti-PD-L1 ICT in a preclinical model and provides mechanistic insights into this synergy.
Patients with KRAS-mutant colorectal cancers do not respond to cetuximab, a monoclonal antibody against EGFR. A new proof-of-concept study presents a bispecific antibody with the ability to trigger EGFR degradation in LGR5+ cancer stem cells, and robust anti-tumor activity in KRAS-mutant and wild-type colorectal cancers.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have revolutionized the treatment of EGFR-mutant non-small cell lung cancer; however, secondary resistance limits their efficacy, emphasizing the need for newer approaches. A study now shows preclinical development of allosteric EGFR inhibitors that overcome acquired therapy resistance.
Severe side effects limit the therapeutic potential of checkpoint control and immunomodulatory antibodies in immunotherapy of cancer. A new study demonstrates that bispecific antibodies directing the immunostimulatory activity of CD40-specific antibodies on dendritic cell subsets may allow a greater therapeutic window of opportunity.
Cellular communication in the tumor microenvironment is crucial for T cell activation; however, the molecular features of the T cell–antigen-presenting cell interaction are still poorly understood. A new study utilizes RNA sequencing of physically interacting cells to reveal that PD-1+CXCL13+ helper T cells in tumors, primed by dendritic cells, are important for the response to immunotherapy.
Two of the first patients with cancer treated with chimeric antigen receptor-modified (CAR) T cells have been cancer free for a decade. A new study uses single-cell sequencing technologies to provide a window into the evolution of their CAR T cells over the course of the ten-year remission period.
The mitochondrial arm of the one-carbon pathway, which is essential for nucleotide synthesis, becomes dominant in cancer cells due to overexpression of several enzymes of the pathway, including MTHFD2. A study now reports on a high-affinity inhibitor of MTHFD2 that starves cancer cells of DNA building blocks and shows potential for selective tumor targeting.
Neutrophils may obtain either pro- or anti-tumorigenic phenotypes depending on environmental cues. A new study reports that cancer radiotherapy induces a neutrophilic response associated with tissue repair and leads to enhanced metastatic spread, highlighting a mechanism by which neutrophils promote metastatic tumor growth.
New research shows that comprehensively characterized patient-derived xenografts (PDXs) of breast cancer can be adapted to high-throughput drug screening and can be used as personalized patient avatars to inform clinical decision-making. This work substantially enhances the repertoire and sophistication of PDXs for research into breast cancer.
Although many potential targets have been identified, effective, specific therapies for metastatic cancers are still lacking. Two studies now identify small-molecule inhibitors of MTDH–SND1 interaction that potently suppress breast cancer progression and metastasis via concerted cancer-cell-autonomous effects and immune modulation.
The architecture of tumor collagen greatly influences tumor biology and therapeutic response. Two new studies identify tumor DDR1 as a central player in stromal collagen deposition and organization in the primary tumor and in disseminated tumor cells, resulting in immune exclusion or sustained dormancy, respectively.
A potential translational strategy to treat brain metastases is the induction or maintenance of proliferative dormancy in tumor cells. A new study shows that dormancy in breast cancer brain metastasis is maintained in the perivascular niche by astrocyte endfoot secretion of laminin-211, causing tumor cell membrane sequestration of YAP.
