Michal Goldberg, Associated Professor of Genetics at the Institute of Life Sciences, The Hebrew University of Jerusalem.
Credit: Special Arrangement
Michal Goldberg, Associated Professor of Genetics at the Institute of Life Sciences, The Hebrew University of Jerusalem, was recently in Bengaluru as a part of a delegation from the university to explore multi-disciplinary research collaborations with several Indian institutes. In an interview with DH’s Udbhavi Balakrishna, Goldberg spoke about the recent advancements in cancer research. Excerpts:
1. Can you share some interesting developments in your research areas?
Genomic instability – the understanding of which is crucial for developing effective cancer treatments – and cancer are dynamic fields with numerous new discoveries and innovations each year.
Recent developments are:
*Genomic techniques, such as whole-genome sequencing and single-cell sequencing, enable the characterisation and detection of mutations associated with genomic instability in cancer at a high resolution.
*Mutational signatures (patterns of somatic mutations or alterations in DNA observed in cancer genomes) associated with DNA repair defects, exogenous mutagen exposure, and endogenous DNA damage processes have been identified, offering insights into cancer progression and aetiology (study into causes of diseases).
*CRISPR/CAS9-based genetic screens have been employed to identify novel genes and pathways involved in the cellular response to DNA damage. These screens enable the systematic knockout or activation of genes to assess their impact on DNA repair, cell cycle regulation, apoptosis, and cancer.
*Novel cancer therapeutic strategies have been developed based on new insights regarding the cellular response to DNA damage. Specifically targeting DNA repair pathways and exploiting vulnerability in DNA damage response-deficient tumours are active research areas for improving cancer treatment outcomes.
*Personalised medicine has also emerged recently, which considers individual variability in genes, environment, and lifestyle for each patient, resulting in tailoring medical decisions, interventions, and therapies.
2. How far have we come in understanding the genetic basis of breast and ovarian cancers, which are two of the most common cancers affecting women in India?
In my opinion, there has been significant progress.
The majority of ovarian and breast cancers occur sporadically and are caused by a combination of genetic, environmental, and lifestyle factors. The identification of genetic drivers and molecular subtypes in ovarian and breast cancers has enabled the development of personalised treatment approaches for these cancers.
Mutations in the BRCA1 and BRCA2 genes are well-established genetic risk factors for both ovarian and breast cancers. BRCA1 and BRCA2 are known to play a role in DNA repair, which has led to targeted therapy based on PARP inhibitors. Both hereditary and sporadic ovary and breast cancers can be treated with this therapy. Mutations in other genes involved in various cellular processes, such as DNA repair, cell cycle regulation, and hormone metabolism, were also associated with increased ovarian and breast cancer risk. These genetic factors have provided insight into cancer development and potential therapeutic targets. However, despite progress, more research is essential to improve our understanding of these cancers and to translate these findings into improved diagnostic tools, targeted therapies, and prevention strategies.
3. Is cancer risk rising amid factors like climate change, global unemployment and inequality, and poverty?
There is no doubt that we are heading toward a period of higher cancer risks, but I do hope that this increase will be balanced at some point in the future. There are several reasons why cancer risks may increase: The proportion of elderly individuals in the population increases as life expectancy increases. Since cancer is an age-related disease, an ageing population is at greater risk of developing cancer. Air pollution, pesticides, and industrial chemicals have been exacerbated by rapid industrialisation and urbanisation. Exposure to these carcinogens increases cancer risk. There has been an increase in the global prevalence of obesity, which is a significant risk factor for several types of cancer. Disadvantaged populations often face barriers to cancer prevention, early detection, and appropriate treatment, leading to disparities in cancer incidence and survival rates. Unemployment, inequality, and poverty can restrict access to healthcare services, including cancer screening, diagnosis, and treatment. A delayed diagnosis and inadequate treatment can result in cancer tumours progressing to more advanced stages, resulting in lower survival rates and a higher severity level. Poverty is associated with stress, which promotes cancer development and progression. Poverty limits access to nutritious food and promotes unhealthy lifestyle behaviours, such as smoking, alcohol consumption, and lack of physical activity, which increase the risk of cancer development.
4. How do we reduce these risks?
It is my belief that cancer risk will decrease if government officials enforce environmental regulations, promote healthy lifestyles with diets and physical activity, and educate people to reduce alcohol and tobacco use. Efforts must be made to improve access to healthcare, implement evidence-based cancer screening programs, and develop innovative cancer therapies.
5. In 2019, you studied a drug that inhibits cancer stem cell growth and reduces tumours. Why is it not a mainstream treatment option yet?
In our study, we found that Spironolactone – a drug typically used to treat high blood pressure, heart failure, and fluid retention – impairs the ability of cancer cells to respond to DNA damage, inhibits cancer cell growth, and is extremely toxic to cancer stem cells (CSCs) that are responsible for cancer relapse and metastasis formation. Our findings demonstrate that CSCs have high levels of DNA double-strand breaks. Mechanistically, we found that Spironolactone does not damage DNA but impairs DNA repair and induces apoptosis (cell death) in cancer cells and CSCs while sparing healthy cells. The treatment of mice with Spironolactone decreased tumour size as well as CSC content. In summary, we show that Spironolactone can be used as an anti-cancer reagent, as it is toxic to both cancer cells and CSCs. Spironolactone is commonly used in the clinic, but its toxicity on cancer and CSCs requires higher concentrations. As a result, additional clinical trials, and the development of a derivative form of Spironolactone that works at lower concentrations may be required. As a result, we chose not to move forward with the translational stage and kept our findings at the basic level. My hope is that someone will invest in this promising anti-cancer drug and make it suitable for clinical use.
6. How can cancer treatment become more affordable and accessible, particularly in developing countries?
To provide affordable cancer treatment options to patients, it is critical to detect cancer early. This is known to increase survival rates. I also suggest providing subsidised cancer treatment programs for the population. For example, investing in community-based healthcare services can improve cancer detection and allow cancer treatment for poor patients living in remote areas. Mobile clinics can bring screening, diagnosis, and treatment services closer to where patients live, reducing barriers to access. Moreover, integrating cancer care into primary healthcare services can ensure that poor patients receive timely diagnosis and treatment. Parallelly, the government should promote education and awareness campaigns regarding cancer prevention, early detection, and treatment options.
7. How close or far off are we from finding solutions to curing cancer completely?
It is difficult to predict when or if we will find solutions to cure cancer completely. There has been a lot of progress in cancer research and treatment over the past few decades, but there is still no definitive cure. While curing cancer completely remains a long-term goal, ongoing research and advances in technology are promising for further improving cancer prevention, diagnosis, and treatment.
8. Are you looking forward to working with any research institutions studying cancer in India?
I am deeply inspired by the potential for collaboration in cancer research with different institutions in India. During my visit to different research institutes in Delhi, Mumbai, and Bengaluru, I saw many opportunities for collaboration. I met many talented researchers in India and learned about the diverse patient population and growing research infrastructure there. I look forward to collaborating with Indian scientists to advance our understanding of cancer.