CRISPR/Cas9 screening enables identification of targets for immunotherapeutics in the setting of lymphoma, leukemia, and other cancers; reviewed by Baoxiang Chen et al. in Trends Mol Med, tinyurl.com/CRISPR-for-Imm…

A review in International Journal of #Oncology discusses mechanisms of senescence‑associated drug resistance in #lymphoma and highlights emerging strategies using senolytics, which are drugs designed to specifically target senescent cells. tinyurl.com/senollytics

Have a great weekend!

CAR-T cells using murine scFv can be targeted by the patient’s immune system; Grauwet et al. (at Harvard) in J Immunother Cancer reveal how to combat this with “stealth transgenes” in the CAR-T cells that reduce their antigen and MHC expression. tinyurl.com/stealthCART

A Blood article from an international research team show that SAMHD1 ara-CTPase activity is intrinsically inhibited by SOX11 in #MCL , which could explain the efficacy of ara-C containing regimens in younger and older patients with MCL. tinyurl.com/SOX11MCL

I wish you a cool relaxing weekend, I shall be making rounds in the MD Anderson hospital.

Exciting prospects for less expensive and off-the-shelf methods to generate CAR-T cells in vivo rather than ex vivo are presented by Short et al. of the University of British Columbia in Trends Pharmacol Sci; tinyurl.com/invivoCART

Megnani et al.’s Cancer Discovery article, Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells, provides compelling evidence & model for how persister dormant cells form & how epidrugs could interfere. tinyurl.com/EpiDormant

Have a great weekend!

The ECHO study is a landmark clinical trial for patients with untreated #mantlecelllymphoma !

Acalabrutinib + bendamustine + rituximab delivered a statistically significant improvement in progression-free survival vs the standard of care in previously untreated #MCL , according to an interim analysis of the ECHO trial. Michael Wang, MD MD Anderson Cancer Center
targetedonc.com/view/acalabrut…

Working with the Baylor College of Medicine, we studied an inhibitor of SRC-3, which is highly expressed in NHL lymph nodes. It is dose-dependently cytotoxic to #MCL cell lines and slows growth of mouse and human ibrutinib-resistant tumors in mice. tinyurl.com/SRC3-MCL

Cancers review from Harvard’s Cabanos and Hata about drug-tolerant persister cells and resistance. Would like to know more about factors that push drug-tolerant persister cells to make the leap into drug-tolerant expanded persister cells. tinyurl.com/DTEPTx

Have a great weekend!

In J Clin Invest, Saunthararajah (tinyurl.com/TxResist) at Cleveland Clinic, commenting on an ALL paper by Aminov et al. (tinyurl.com/ALLresist), reviews how resistance in B-cell malignancies arises through both Darwinian and Lamarckian mechanisms.

Saunthararajah (tinyurl.com/TxResist) notes that the Darwinian model for therapy resistance involves therapy-induced selection of malignant cells with mutations or deletions, while the Lamarckian model involves therapy-induced changes that are inherited epigenetically.

Our laboratory enjoyed all the research at the 2024 #AACR Conference. Even better, Dr. Vivian Jiang got to share her work on YX0798 for Mantle Cell Lymphoma ( #MCL ).

Liang et al. of Nanjing Med Univ found that many #MCL patients had elevated arginine methyltransferase PRMT5, which upregulated MYC; this promoted activation of key lipid metabolism genes SREBP1/2 and FASN, associated with poorer patient outcomes. tinyurl.com/PRMT5

Our laboratory had a great time at the 2024 #AACR Conference. Even better, Dr. Yang Liu got to share his work on BTM-3566.

Our Phase I TRANSCEND trial demonstrated that Liso-cel results in consistently high objective response rates and complete response rates in patients with heavily pretreated R/R #MCL , including those with high-risk disease characteristics. tinyurl.com/LISO-TRANSCEND