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Evol Science is a startup biotechnology company focused on identifying and therapeutically exploiting mechanisms of cancer cell resistance, which we discover using our proteo-genomic and proprietary AI-driven data analytic platform. 

Evol’s platform identifies and targets cancer cell drug resistance, acquired and intrinsic, accelerating and de-risking drug development and clinical translation. We generate a novel pipeline for our BioPharma partners and license out our IP, expanding their patient reach. Evol’s first biological discovery has generated multiple novel drug combinations to treat late-stage, RAS-driven cancers including metastatic melanoma, pancreatic, colorectal, breast, and lung. We expect to have our first combination in proof-of-principle clinical trials in the first half of 2020. Our goal is to make the deadliest cancers survivable.

Recent Research:


“Methotrexate sensitizes drug-resistant metastatic melanoma cells to BRAF V600E inhibitors dabrafenib and encorafenib.”

Kayleigh C. Ross, Kevin F. Chin, Daehwan Kim, Christopher D. Marion, Timothy J. Yen, Vikram Bhattacharjee*
2018. DOI: 10.18632/oncotarget.24341


Acquired resistance of metastatic melanoma (MM) tumors to BRAF V600E inhibitors (BRAFi's) is commonplace in the clinic. Habitual relapse of patients contributes to <20% 5-year survival rates in MM. We previously identified serine synthesis as a critical detrminant of late-stage cancer cell resistance to BRAFi's. Pre-treatment with DNA damaging agent gemcitabine (a nucleoside analog) re-sensitized drug-resistant cancer cells to BRAFi's dabrafenib and vemurafenib. Importantly, the combination treatments were effective against BRAF wild type cancer cells potentially expanding the clinical reach of BRAFi's. In this study, we identify the antifolate methotrexate (MTX) as a sensitizer of acquired- and intrinsically-resistant MM cells to BRAFi's dabrafenib and encorafenib. We identify a novel, positive correlation between dabrafenib treatments and repair delay of MTX induced single-strand DNA (ssDNA) breaks. Cells arrest in G1 phase following simultaneous MTX + dabrafenib treatments and eventually die via apoptosis. Importantly, we identify RAS codon 12 activating mutations as prognostic markers for MTX + BRAFi treatment efficacy. We describe a method of killing drug-resistant MM cells that if translated has the potential to improve MM patient survival.

AACR Journals - Molecular Cancer Therapeutics

"Identification of the serine biosynthesis pathway as a critical component of BRAF inhibitor resistance of melanoma, pancreatic, and non-small cell lung cancer cells"

Kayleigh C. Ross, Andrew J. Andrews, Christopher D. Marion, Timothy J. Yen and Vikram Bhattacharjee*
Published OnlineFirst May 12, 2017. DOI: 10.1158/1535-7163.MCT-16-0798


Metastatic melanoma cells commonly acquire resistance to BRAF V600E inhibitors (BRAFis). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemurafenib (BRAFi) treatment in sensitive versus acquired resistant melanoma cells. Ablation of PHGDH via siRNA sensitized acquired resistant cells to vemurafenib. Inhibiting the folate cycle, directly downstream of serine synthesis, with methotrexate also displayed similar sensitization. Using the DNA damaging drug gemcitabine, we show that gemcitabine pre-treatment sensitized resistant melanoma cells to BRAFi's vemurafenib and dabrafenib. We extended our findings to BRAF WT tumor cell lines that are intrinsically resistant to vemurafenib and dabrafenib. Pre-treatment of pancreatic cancer and non-small cell lung cancer cell lines with sublethal doses of 50nM and 5nM of gemcitabine respectively, enhanced killing by both vemurafenib and dabrafenib. The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFi's in combination to kill previously drug resistant cancer cells, creating the translational potential of pre-treatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT.

* - Corresponding Author