The BACR 60th anniversary meeting was held from 26 – 28 June 2022 at the NTU Conference and Events, Nottingham, UK. The meeting had 5 themed sessions of oral presentations with each session comprised of 6-7 talks. The themes included new technologies, engineering and imaging; tumour microenvironment and immunotherapy; resistance to therapy; signalling networks; and disruptive science and the future. Most of the talks were from cancer experts or scientists who have vast experience and knowledge in cancer research and therapeutic fields. There were also talks from speakers who received differing awards recently owing to the novelty of their research findings. I was amazed by the loads of scientific information and research advancements delivered by each of these speakers. There were also a few talks from PhD students from various universities which became a source of inspirations to me especially on how we can contribute to therapeutic and translational cancer research.
The meeting was started by introducing the new technologies, engineering and imaging modalities now available in the cancer research field that will greatly contribute to cancer diagnostics and therapeutics. The concept of ‘cold tumours’ was introduced which was then linked to the importance of sensitizing tumour cells before targeted tumour cell killing. This is done by activating the immune cells prior to initiating the targeted therapy to make tumour cells more susceptible, and one of the amazing methods introduced was the use of oncolytic virus that will elicit high T cell responses. In addition various innovative imaging modalities were developed and introduced which will aid cancer detection and treatment such as the integrative imaging-OMIC combination that detects patients with high risk of early recurrence and the ex vivo imaging of patients’ biopsies to screen for the best drug response in order to achieve precision medicine.
Norain Binti Ab Latif at the BACR 60 Anniversary Meeting in Nottingham, June 2022
The second session of the meeting brought audience to the basis of tumour microenvironment and the role of the immune cells in tumour progression. The extracellular matrix (ECM) component mainly the collagen and the fibroblastic cells within the tumour periphery known as the cancer-associated fibroblast (CAF) are among key players in tumour development within a tissue. Stiff ECM due to a high and aberrant collagen deposition may drive cancer aggressiveness. Similarly, the CAF are re-programmed to support tumour growth and invasiveness. These cells produce high level of the enzyme matrix metalloproteinase (MMP) that degrades the ECM and modulates tumour invasion. In addition, infiltration of immune cells such as the neutrophil, macrophages, myeloid-derived suppressor cells (MDSCs) and dendritic cells in an inflammatory response will create a premetastatic environment permissive for tumour cell arrival and growth in the tissues. In contrast, elevating the infiltration of CD8+ T cells and natural killer (NK) cells would aid tumour killing. Therefore, identifying the key regulators of the immune cells is a crucial step in tumour eradication, which is the strategy used in cancer immunotherapy.
In cancer treated with radiotherapy, radiobiological hypoxia (RH) often occurs leading to tumour resistance and has become a major barrier for effective radiotherapy. RH causes replication stress and induces both the unfolded protein response (UPR) and DNA damage response (DDR), two hypoxia-induced signalling pathways that promote tumour survival and metastasis despite treatment. Similarly in immunotherapy, children and young people with B cell acute lymphoblastic leukaemia are now commonly treated with the chimeric antigen receptor T-cell (CAR-T) therapy. However, many patients developed resistance to this treatment and had tumour relapses. Recent in vivo finding revealed JAK/STAT and Interferon-gamma (IFN-ƴ) receptor loss promotes resistance to CAR-T therapy. Furthermore, in non-small cell lung cancer, acquired resistance to PD(L)-1 treatment is also associated with dysfunctional IFN response. Another interesting insight in this cancer resistance session is also the role of APOBEC3 in driving mutagenesis in multiple cancer types. Increased expression of APOBEC3B with tyrosine kinase inhibitor (TKI) therapy in patients with EGFR mutant lung cancer increases the number of mutations and leads to cancer resistance. All these lead to the development of treatment strategies to resolve cancer resistance to therapy. Treatment strategies designed to target specifically the DDR pathway and to augment NK therapy by inducing mitochondrial apoptosis are underway and are highly promising.
In the signalling networks session, multiple signalling pathways are currently developed as the potential targets for cancer therapy. This includes the p38α stress kinase signalling and the cell death-associated inflammatory pathway. The p38α for example not only is a key regulator of stress response, but also works as a tumour suppressor in many tissues. However it is not normally silenced in cancer cells compared to the other tumour suppressor genes. This protein affects various protein kinases and its inhibition enhances the response of cancer cells to chemotherapy. On another insight, inducing mitochondrial outer membrane permeabilization (MOMP) will increase the activity of caspase proteases and may cause the unfavourable genomic instability. However inhibition of caspase activity following MOMP will trigger the caspase-independent cell death (CICD) and promotes tumour growth inhibition. In addition, the major transcription factor in inflammatory response, Nuclear factor kappa B (NF-κB) has also become a promising target in small cell lung cancer, while the role of phosphoinositide 3-kinase (PI3K) signalling in prostate tumour progression is currently further investigated.
Finally, the last session of the meeting once again highlighted the use of advanced imaging for cancer diagnosis with high precision which aims for precision treatment. Imaging mass spectrometry for example generates 3D images with advantages on distance and cellular neighbourhood around the tumour mass allowing deep tumour profiling and targeted therapy. This imaging modality allows the use of up to 40 markers at one time enabling neighbourhood clustering to identify cellular communities. Meanwhile, molecular profiling of patients’ liquid biopsies enables the detection of personalised mutation markers in cancer detection. Analysis of epigenetic modification of cell-free circulating DNA (methylation, etc) could reveal the origins of these DNA and is important in detecting tumour residual and recurrences. There was also a treatment strategy focussing on targeted protein degradation in cancer by manipulating the ubiquitin-proteasome system, and also an approach that uses the KRASG12C inhibitor in KRAS mutation in patients that developed resistance which increases binding of this protein to GDP (instead of GTP) to switch off its activity.
Consequently, this conference meeting covered a wide scope of cancer topics ranging from understanding the tumour and its microenvironment, modifications in the molecular and signalling pathways that could become potential therapeutic targets, the role of the immune system in cancer development and treatment, new technologies for cancer diagnosis and detection of relapse as well as potential strategies to overcome cancer resistance. The meeting fed especially young researchers like me with lots of insights on cancer research development and the on-going translational investigations which are crucial for designing better treatment and increasing the survival of cancer patients. Apart from gaining more knowledge and the opportunity to present my work through a poster presentation, the meeting also became a platform for me to network with many people in this cancer field, both the professionals and PhD students from other universities. I am definitely looking forward to attending the next BACR conference next year. Therefore, I would like to deeply thank the BACR for the student travel award, which without one I probably wouldn’t be able to attend this conference meeting.
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