Science Writing Prize 2024 - The Seemingly Endless Quest to Target Cancer's Weaknesses: The Search for Multiple Achilles’ Heels.

Cancer is a concept that has, unfortunately, become all too familiar to many of us. The fears, the struggles, the tears - we've been through it all. My own motivation for studying cancer is because my mother and her sisters all succumbed to it (each with a different type, no less). It doesn’t help that, traditionally, the “cure” hurts as much as the disease; we’ve long had to grapple with balancing the toll of chemotherapy and radiation therapy with the promise of having even just a bit more time with our loved ones. But what if there's an alternative approach that can offer better odds while also being less painful for patients? Let's talk about our ongoing quest to target cancer's weaknesses, the battles we’ve won, and why we shouldn’t lose hope against this relentless adversary.

Think of cancer as a difficult video game boss. It's tough, it's cunning, but it's got its own set of weaknesses. You fight it over and over and fail, but over time you learn its moves, discover chinks in its armour, and form a strategy to exploit those chinks. That's precisely what targeting weaknesses in cancer is all about - finding those hidden vulnerabilities.

Before we go any further, let's break it down into simple terms. Cancer isn't just one villain: it's a whole gang of them. Each type of cancer has its own unique traits, making each one a tough nut to crack. The silver lining is that every gang member has its own quirks that we can use to our advantage.

Cancer researchers are like detectives on the case. They're peeling back the layers to figure out what makes these troublemakers tick. Decades of hard work have shown us that different cancers have certain vulnerabilities we can exploit. Here are some of the most promising ones:

1. Genetic Gaffes: Many cancers are born from genetic mutations. These are like corrupted or misspelled instructions that turn normal, healthy cells into rogue, harmful ones. What if we could develop special treatments to target just those mutations? It's like aiming for the bullseye and avoiding as much collateral damage as possible.

    

2. Nutritional Nemeses: Cancer cells are picky eaters. They gobble up specific nutrients in strange ways. By messing with their food supply, we can starve them and slow down their growth.

    

3. Stealth Savants: Some cancer cells are like ninja assassins, sneaking past our body's defence system. Using immunotherapy drugs as our trusty sidekicks, we can give our immune system the extra push it needs to sniff out and take down these elusive enemies.

    

4. Bloodflow Blockade: Tumours need blood to thrive, they consume nutrients faster than normal cells, and they're pretty good at building their own blood supply. So, why not cut off their lifeline? Anti-angiogenic drugs do just that, depriving tumours of the food and oxygen they crave.

    

5. DNA Repair Blunders: Some cancer cells can't fix their DNA properly. They make mistakes and can't repair them. This helps them evolve and adapt into deadlier versions of themselves, but also makes them vulnerable to overwhelming amounts of damage. Radiation therapy and certain drugs create even more chaos in their DNA, leaving these cells in a tangled mess.

    

6. Epigenetic Shenanigans: Cancer cells meddle with the gene control system that supervises which genes get turned on and off at any given time. But we've got treatments that can set things back on the normal track.

Now, knowing these chinks in the armour of cancer cells is one thing, but turning this knowledge into action is where the real magic happens. These targeted treatments are like guided missiles - they lock onto the vulnerabilities we've uncovered and go straight for the kill, sparing healthy cells.

 Let's talk about some success stories that give us hope:

• Imatinib (Gleevec): This one's a lifesaver for those dealing with chronic myeloid leukaemia (CML). It homes in on the specific genetic mutation causing the trouble, transforming a death sentence into a manageable condition.

   

• Lynparza (Olaparib): Not only does Lynparza interfere with a protein that cells need to repair their DNA, it does so in a way that creates even more DNA damage. This is particularly devastating in cancers that already have trouble fixing their DNA, and Lynparza has been a godsend especially in breast and ovarian cancer.

   

• Immunotherapy: These game-changers, like Keytruda and Opdivo, reawaken our immune system, reminding it of its mission to fight off invaders. They've brought new hope for folks battling melanoma, lung cancer, and kidney cancer.

   

• Herceptin (Trastuzumab): Herceptin takes the spotlight for some breast cancers that have been playing hard to get. It latches onto the HER2 protein that these cancers flaunt and stops them in their tracks.
  

Of course, it's not all smooth sailing. Cancer is a tricky opponent that can adapt and become resistant to targeted therapies. Not all cancers have clear-cut weaknesses we can exploit, and some might need a combination of treatments. But at least we're not in the dark anymore, blindly throwing punches. In my own work, I use libraries that contain hundreds, if not thousands, of drugs on cancer cells, hoping to find vulnerabilities that we can attack with stronger, better drugs of our own. This is just one of many strategies that cancer researchers all over the world are trying as part of the collective fight to defeat cancer.

The road ahead is still long, and we've got a lot of ground to cover. But research is charging forward relentlessly, uncovering new vulnerabilities, making targeted therapies even more precise, and, in some cases, offering personalised treatment plans. There is no “magic bullet” for cancer because cancer is not just one villain to overcome. Instead of attempting that impossible quest, we’re approaching the problem from a different perspective and aiming towards finding a different Achilles’ heel for each situation. The war is far from over, but we’re winning battles and approaching victory one step at a time.

This piece won the 2024 Mel Greaves Science Writing Prize.

Dr Kirsten Lopez is a postdoctoral scientist from the Philippines. Prior to joining the ICR in 2020, she obtained her undergraduate degree in Molecular and Cell Biology from Singapore and worked there as a scientist for several years in both academic and pharmaceutical research. She received her PhD in Oncology at the University of Oxford and is currently a Postdoctoral Training Fellow in the Target Evaluation and Molecular Therapeutics team.

Her research is primarily focused on identifying novel strategies to treat cancer by exploiting specific weaknesses that can arise from cancer-driving mutations, thus taking advantage of a concept known as synthetic lethality. Her current work involves finding vulnerabilities in cancers that have mutations in a particular family of DNA repair genes, enabling the preferential killing of mutant cancer cells while sparing normal cells from harm.