UCLA researchers have developed a CAR-NKT cell therapy that has shown to be more effective than current immunotherapies at fighting cancer in tumor samples from late-stage triple-negative breast cancer patients.

While personalized treatments can cost six figures and require weeks to manufacture, this therapy can be mass-produced from donated blood stem cells and stored ready-to-use at about $5,000 per dose.

The same cell product could potentially be used to treat multiple solid tumors like ovarian, pancreatic and lung cancers — all of which express the protein mesothelin.

A new preclinical study has disentangled the molecular pathways that permit breast cancer tumors to metastasize and evade the effects of immunotherapies. The experiments also showed that approved drugs that inhibit an enzyme named PARP1 sensitized breast tumors to immunotherapeutic antibodies, hinting that PARP1 inhibitors could be repurposed to improve clinical outcomes. Although scientists have made huge strides in the treatment of breast cancer, it is still a leading cause of death among women. There is a dire need for new treatments, especially for triple-negative breast cancer (TNBC). This type of cancer has few treatment options and will often become resistant to both chemotherapy and newer immunotherapies such as checkpoint blockade. Previous research has suggested that the YAP1 protein and the TEAD family of transcription factors support the metastasis of breast cancer as well as its ability to resist immunotherapies. However, YAP has typically been considered “undruggable,” and more studies are needed to discover drugs that can indirectly target YAP1 and TEADs. Now, Yibo Guo and colleagues identify PARP1 as a previously unknown third player in the YAP1-TEAD pro-tumor machinery. Specifically, they found that PARP1 triggered the formation of complexes between YAP1 and the protein TEAD4 by biochemically modifying the latter. This in turn shielded YAP1 from being marked and degraded by other enzymes, thus sustaining its tumor-supporting effects. Guo et al. also found that treatment with olaparib and veliparib – two FDA-approved PARP inhibitors – inhibited the formation of YAP1-TEAD4 complexes and facilitated the degradation of YAP1. The drugs also augmented the ability of anti-PD-L1 immunotherapy to slow the growth of tumors in the mouse models. An analysis of the Cancer Genome Atlas confirmed that the expression of PARP1 rose alongside YAP1 and PD-L1 in breast tumors from patients, indicating that this mechanism is active and potentially targetable in humans.

New research from Cold Spring Harbor Laboratory's dos Santos lab shows that inhibiting the BPTF protein in mice can slow or stop the spread of ER+ breast cancer and keep tumors vulnerable to common hormone therapy. The team’s findings could someday help prevent breast cancer recurrence and lead to better patient outcomes.