Khalid Saeed's dissertation shows why it pays to be an early adopter

M.Sc. Khalid Saeed’s thesis entitled "Functional testing of urological cancer models by RNAi and drug libraries” focuses on identifying novel future treatment strategies for prostate, renal and kidney cancer. His doctoral dissertation will be publically examined today on 13 August, with the permission of the Faculty of Medicine of the University of Helsinki.

Khalid Saeed graduated from the University of Karachi, Pakistan, in 2007 having biotechnology as his major subject. After spending a few years at the Uppsala University and Karolinska Institute, he joined Professor Olli Kallioniemi’s research group at FIMM in 2010, first through the Marie Curie Initial Training Network “Prostate Research Organizations-Network of Early Stage Training” programme PRO-NEST. The work has been co-supervised by Olli Kallioniemi, Päivi Östling and Taija af Hällström.

The overall goal of Khalid’s thesis was to generate molecular profile and drug testing data using patient-derived cancer cells. His proof-of-concept studies show that this kind of data can be used to help clinicians in treatment decision and to facilitate the early selection of the best drug candidates for clinical development.

Khalid’s thesis project is part of FIMM’s “Individualised systems medicine in cancer” Grand Challenge programme. Most of the work related to this grand challenge published thus far has, however, focused on haematological cancers. Since Khalid has worked with solid tumors, establishment of patient-derived primary cell models was an important part of the thesis.

Functional studies are often done in conventional cell lines but implementing the results for drug repurposing, development and precision medicine requires patient-derived cells.

- Khalid Saeed

Khalid’s PhD thesis consists of three scientific publications describing the results of two systematic screening-based projects. The first project focused on identifying genes that sensitize prostate cancer cells during androgen-deprivation using an RNA interference screen. He was able to identify a novel androgen receptor-interacting protein, HSPBAP1, as a possible prostate cancer drug target.

Although androgen receptor is central to prostate cancer biology, targeting it alone is not effective enough and development of combinational therapies is of outmost importance.

The second screening project piloted drug-response profiling in patient-derived cells. Khalid was especially interested in intra-tumor heterogeneity and thus explored the drug sensitivity from multiple sites in a tumor with the aim to target multiple tumor subclones.

Most precision cancer medicine efforts are based on the identification of oncogenic driver mutations by genome sequencing. We believe and have emerging evidence that this will miss therapeutic opportunities. Thus additional technologies, such as the ones used in this thesis, should be applied more widely

These studies have also encouraged Group Kallioniemi’s clinical collaborators to initiate a clinical trial for development of diagnostics and treatment of urological cancers.

 

In the future, I expect that the implementation of improved patient-derived cell culture methods in early phase of drug discovery could enable better assessment of drug efficacy and toxicity before its entry into the clinical trials. This would have implications for cancer diagnosis, tailoring of drugs, designing of effective drug combinations and precision cancer medicine

Khalid characterizes himself as a realistic optimism. This, combined with his hardworking nature, have been of great value during his PhD thesis project. Outside of science, Khalid is a passionate cricketer and a registered player for the league games organized by the Finnish Cricket Association.

Khalid’s future plans are not yet settled but he would like to continue working with cancer (precision) medicine during his post-doctoral career, be that in academia or industry.

M.Sc. Khalid Saeed will defend his doctoral dissertation entitled "Functional testing of urological cancer models by RNAi and drug libraries" at the Faculty of Medicine, University of Helsinki, on 13 August 2018 at twelve o'clock noon. MD, PhD Sakari Vanharanta, University of Cambridge, will serve as the opponent, and Professor Satu Mustjoki as the custos. The public examination will take place at the following address: Biomedicum Helsinki, luentosali 3, Haartmaninkatu 8.

The dissertation is also available in electronic form through the E-thesis service.