Where Ideas Grow

Student receives Fulbright grant to study resistance to colorectal cancer therapies

Student Flávia Martins, from the Doctoral Program in Biomedicine at the Faculty of Medicine of the University of Porto (FMUP), and developing research at the i3S, recently received a Fulbright Scholarship that will allow her to develop part of her PhD in the United States and learn nanoimaging techniques to study resistance to colorectal cancer therapies.

Flávia Martins will have the opportunity to spend around six months at the Center for Physical Genomics and Engineering at Northwestern University (Illinois), in the group led by researcher Vadim Backman. This collaboration, she explains, “followed on the preliminary results obtained during my doctoral project, which revealed changes in the organization of DNA and the reprogramming of gene expression as possible mechanisms of resistance to anti-KRAS therapy in colorectal cancer”.

KRAS is the most frequently mutated oncogene in cancer. These genes are present in almost half of colorectal cancer patients and are negative predictors of treatment response. Due to its enormous relevance in various types of cancer, KRAS is considered one of the main therapeutic targets. However, the development of therapies to inhibit KRAS has been one of the great challenges in oncology. Although mutations were described approximately 40 years ago, it is only recently that we have available in the clinic a drug to inhibit one of the mutated forms of KRAS. However, clinical data demonstrate that tumor cells treated with this KRAS-directed therapy are able to tolerate the treatment and develop resistance mechanisms very quickly that allow them to continue to grow. It is therefore essential to identify the mechanisms that allow these cells to overcome KRAS inhibition and resume tumor growth.

In Professor Backman’s laboratory, Flávia Martins says “I will have the opportunity to deepen and complement these results through the characterization of the three-dimensional organization of DNA in the nucleus after activation and inhibition of KRAS using new nanoimaging techniques developed in her group”.

For Flávia Martins, who is developing her PhD in the group “Epithelial Interactions in Cancer”, under the supervision of researcher Sérgia Velho, these six months in the United States represent an “opportunity to learn techniques that do not yet exist in Portugal and, eventually, implement them in i3S. It also creates conditions to establish a new collaboration between i3S and a renowned US university”. Furthermore, she adds, “experiencing the reality of a laboratory outside Portugal will certainly help me to grow professionally and personally”.